A patient is referred to as "suffering from asymptomatic neurosyphilis" when the cerebrospinal fluid reveals findings indicative of the infection, but no observable symptoms of neurological nature [9]. An infected person can lack syphilis-related symptomatology at any point of the infection's course over the years, but this is more common for the early phase.

Neurosyphilis initially presents with profound meningitis, which can be suspected when the patient experiences nausea, vomiting, headache, photophobia, occasional seizures, and cranial nerve palsies [10]. Meningitis attributed to neurosyphilis mostly takes place subsequent to lack of management and therapy of early syphilis [11] [12]. The facial nerve is usually the first one to be damaged, followed by the vestibulocochlear nerve, abducens nerve, and optic nerve.

Meningovascular syphilis, on the other hand, is characterized by inflammation of the vessels in the central nervous system, this leads to the formation of thrombi and infarcts. Patients in their early adulthood who suffer from meningovascular syphilis usually present with the so-called "stroke syndrome", namely a cerebrovascular event mostly in the middle cerebral artery. This type of syphilitic disease commonly needs up to a decade from the primary infection in order to be revealed [13] [14]. Additional symptomatology that can arise early in the course of the infection includes vertigo, headaches, and insomnia. The clinical characteristics of this type of syphilis tend to fluctuate, dictated by the arterial branch that is affected each time. Indications of severe neurological damage are hemiplegic phenomena, aphasia, hemianopsia (homonymous) and sensory disruption in the left or right side of the body. Lastly, since spinal blood vessels are also potentially subject to thrombosis, cases of patients presenting with paralysis, loss of sphincter control and atrophic muscles are often observed [15].

Parenchymatous syphilis is subdivided into general paresis (paretic neurosyphilis) and tabetic neurosyphilis ("tabes dorsalis" or progressive locomotor ataxy).

General paresis

After the initial infection with Treponema pallidum, general paresis may require up to thirty years in order to start producing symptoms. This medical entity is a concurrent encephalitis and meningitis, usually restricted to the temporal and frontal lobes. Headaches, insomnia or interrupted sleep, absentmindedness and a fluctuating temper may appear in the beginning. As the disease progresses, the patient starts to become disoriented, delusional, exhibits epileptic symptoms, alongside cognitive and emotional dysfunction. General paresis may be easily misdiagnosed as a strictly psychiatric condition, as psychotic and manic episodes are interchanged with depressive periods of times. Another sign of general paresis are the Argyll-Robertson pupils: the pupils do not react to light, but change their size in order to eye a close object [16].

Tabes dorsalis

Tabetic syphilis is a distinct, rather rare type of syphilitic infection, which may arise many years after the original contraction of Treponema pallidum. The circumstances under which this clinical entity arises are not yet known, however, it is expected to occur after twenty or thirty years after the infection.

This complication involves profound neurologic symptomatology and signs, including ataxia, paresthetic phenomena, atrophy and palsy of the optic nerve [17], Argyll-Robertson pupils, poor proprioception and reduced reflexes. The basic pathophysiologic alteration that accounts for the aforementioned clinical picture centers around a considerable degenerative process of the dorsal roots and spine. Neurologic symptoms are not the only observable ones, however; epigastralgia, emesis and nausea are present in 15% of the patients who are affected by the tabetic type of syphilis and is attributed to dysfunction of the internal organs.

Another potential manifestation of syphilis is ocular syphilis [18], which leads to panuveitis, retinitis, papillitis or vitreitis, practically affecting every structure of the eye [19] [20]. Patients experience impaired vision and photophobia. These manifestations typically indicate progressed disease.

• Epilepsy

  “There’s a lot of research showing that patients with epilepsy—men and women—do not conceive children at the same rate as those without epilepsy,” said study co-author Cynthia Harden, MD. [practicalneurology.com]

  At first, symptomatic epilepsy in the context of alcoholism was suspected. During the following days… CONTINUE READING Highly Cited This paper has 24 citations. REVIEW CITATIONS From This Paper Figures, tables, and topics from this paper. [semanticscholar.org]

  Brain Boost Sound Advice The link between hearing loss and cognitive decline PICTURES OF YOU The Bright Side After epilepsy derailed her dream of being a dancer, Susan Cruz hopes to teach dance to children. [patients.aan.com]

  Intractable epilepsy as the initial manifestation of neurosyphilis [22]. [wikigenes.org]

  Epilepsy Res 2004, 59 :67–70. PubMed CrossRef Google Scholar 16. Jacquemin GL, Proulx P, Gilbert DA, et al. : Functional recovery from paraplegia caused by syphilitic meningomyelitis. J Spinal Cord Med 2002, 25 :133–137. PubMed Google Scholar 17. [link.springer.com]

• Weight Loss

  The patient reported asthenia (abnormal loss of strength), weight loss, and bilateral red, painful eyes. He also reported severe vision loss, which had been progressive. It was the vision loss that prompted his visit to an emergency room. [pharmacytimes.com]

  Secondary Syphilis About 2 to 10 weeks after the first sore appears, you may develop the following: A skin rash that causes small, reddish-brown sores Sores in your mouth, vagina, or anus Fever Swollen glands Weight loss Hair loss Headache Extreme tiredness [webmd.com]

  During this stage, a person may feel sick and experience fever, sore throat, fatigue, weight loss, and headache. A generalized swelling of the lymph nodes ( generalized lymphadenopathy ) is also common. [alzheimers.about.com]

• Fecal Incontinence

  Inability to control urine or stool (urinary or fecal incontinence). Most forms of neurosyphilis take years to develop and can be life-threatening. [cigna.com]

  Inability to control urine or stool (urinary or fecal incontinence). How is neurosyphilis treated? Antibiotic treatment cures the syphilis infection and stops the progress of neurosyphilis. [healthy.kaiserpermanente.org]

• Oral Ulcers

  ulcer in a patient who is human immunodeficiency virus positive: a case report. ( 28499407 ) Njiru E....Kigen G. 2017 40 Incidence of asymptomatic neurosyphilis in serofast Chinese syphilis patients. ( 29133821 ) Cai S.N....Lun W.H. 2017 41 Neurosyphilis [malacards.org]

• Heart Disease

  Chlorpromazine also is known to cause QTc prolongation, especially in patients with heart disease. Medication change A serum rapid plasma reagin test is non-reactive, but Treponema pallidum particle agglutination is positive. [mdedge.com]

• Jaundice

  Eventually, babies can develop complications of many organs including: Enlarged liver Jaundice Discharge from nose Swollen glands Bone abnormalities Brain (neurological) problems See your child’s pediatrician right away if she develops an unusual discharge [webmd.com]

  […] untreated, the symptoms may include: Liver and spleen enlargement Petechia (purplish skin spots caused by ruptured capillaries) Profuse nasal drip (known as syphilitic "snuffles") with highly infectious mucus discharge Neurosyphilis Lung inflammation Jaundice [alzheimers.about.com]

• Alopecia

  Other telltale symptoms include unexplained hair loss (syphilitic alopecia) and cracked lesions on the corner of the mouth (fissure cheilitis). [alzheimers.about.com]

  He didn’t have any other clinical sign such as chancre or macular, maculopapular, or pustular rash, and mucous patches and alopecia. But we considered oculomotor nerve palsy associated with neurosyphilis based on the Argyll Robertson pupil. [omicsonline.org]

  Secondary syphilis consists in a macular, maculopapular or pustular rash involving often the palms and soles and alopecia, fever, lymphadenopaty and central nervous system (CNS) disturbances, appearing within weeks to months after untreated primary infection [tmj.ro]

  (2) mucous patches (gray, superficial erosions or plaques on the buccal mucosa and tongue, under the prepuce and on the inner labia; (3) split papules (fissured, nodular lesions at the angle of the lips and in the nasolabial folds); and (4) patchy alopecia [hindawi.com]

• Skin Disease

  Author information 1 Guangdong Provincial Center for STI & Skin Diseases Control and Prevention, Guangzhou 510091, China. 2 Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangzhou, China. 3 Guangdong Provincial Center for STI & Skin Diseases [ncbi.nlm.nih.gov]

  We then distributed the list of cases to the 21 prefecture-level skin disease and STD control centres, based on the location from which the reports came from. [nature.com]

  Diversity of skin lesions with a combination of signs and symptoms are often confused with many other diseases. All the skin lesions in secondary syphilis are infectious as they harbor bacteria. [clinicaladvisor.com]

  […] and is described in the Bible and the writings of Hippocrates.6 The sufferings of Job, or male de Santo Job, were particularly identified with the great pox.2 (Saint Job is the patron saint of melancholies, lepers, and those with skin diseases.2) However [healio.com]

• Hearing Impairment

  […] and vision impairment. [jmedicalcasereports.biomedcentral.com]

• Pupillary Abnormality

  Physical examination revealed no cranial nerve palsies or pupillary abnormalities. Power was decreased on flexion of the right hip and knee and on extension of both knees. [cmaj.ca]

  Late neurologic symptoms include pupillary abnormalities, hypotonia, seizures, and involvement in cranial nerves II, III, VI, VII and VIII (Simon, 1985). [priory.com]

  abnormalities are more common in tabes .[9] Arteritis associated with syphilitic invasion can cause strokes that affect vision and eye movement. [eyewiki.aao.org]

  […] as did "attacks" of hemiplegia, monoplegia, aphasia, or hemianopia.22 Patients died as a result of seizures (common in advanced cases), aspiration, or infections.25 Neurologic signs were present even in the early stages of general paresis, including pupillary [healio.com]

• Blepharoptosis

  He had right paralytic blepharoptosis, and both pupils were fixed and both pupils were not observed direct and indirect reflex and anisocoric. We observed Argyll Robertson pupil. [omicsonline.org]

• Delusion

  A Pakistani man aged 60 years presented with personality change, aggression, paranoid delusions and sexual disinhibition while being treated for severe chest sepsis in intensive care. [ncbi.nlm.nih.gov]

  Summarized by the mnemonic PARESIS: P = Personality changes A = Affect R = Reflexes (hyperreflexia) E = Eye (Argyll Robertson Pupil – reacts to accommodation, not light – aka “Prostitute’s Pupil”) S = Sensorium – hallucinations, delusions I = Intellect [errolozdalga.com]

  A 46-year-old previously healthy man was referred to a psychiatric department after debuting with persecutory delusions. He had symptoms of Parkinson's disease as well as a significant impairment of memory and cognitive function. [pure-portal.regsj.dk]

  Symptoms include abnormal gait, blindness, dementia, hallucinations and delusions, sharp stabbing pain, depression, headache, incontinence, irritability, numbness in the lower extremities, poor concentration, seizures, stiffness in the neck, speech changes [jlhede.wordpress.com]

• Euphoria

  The wife described hypomaniacal behavioral disturbances that appeared in the same time, with euphoria and logorrhea of the moriatic type, the patient’s previous personality being usually sober and reserved. [tmj.ro]

  In a five year follow-up of patients with neurosyphilis, 50% of patients showed resolution of disorientation, convulsions, tremors, incontinence, euphoria and depression, while only 25% of patients showed resolution in delusions, hallucinations, and impaired [priory.com]

• Headache

  At the time of discharge his headache and neck stiffness resolved, dysesthesias were decreased in intensity. MRI findings here revealed T2/FLAIR hyper intensities with generalized cerebral atrophy. [n.neurology.org]

  Penicillin G (PCG) was administered, and his facial nerve function and headache improved. However, left-side hearing loss worsened temporarily, which was assumed to be a Jarisch-Herxheimer reaction. [ncbi.nlm.nih.gov]

  During the whole period of this illness, the patient continued to have headaches on and off, and again the nature of this pain was somewhat different from that of her usual migraine headache. 4. [hindawi.com]

  A subacute encephalitic prodrome is present, with headache, vertigo, and psychological abnormalities. The CSF usually reveals elevated protein levels, lymphocytic pleocytosis, and a glucose level within the reference range. [ajnr.org]

• Seizure

  We report a 33-year-old Japanese man who suffered from repetitive generalized tonic-clonic seizures which were medically intractable. [ncbi.nlm.nih.gov]

  Case report A 48–year–old man was brought to our hospital emergency room by ambulance because of generalized seizures. He did not have any previous history of seizures or epileptic attacks. [austinpublishinggroup.com]

  General paresis is characterized by progressive DEMENTIA; DYSARTHRIA; TREMOR; MYOCLONUS; SEIZURES; and Argyll-Robertson pupils. [fpnotebook.com]

  Thus 11% of the neuropsychiatric group also had seizures, and 43% of the seizure group and 29% of the CVA group also had a delirium. [jnnp.bmj.com]

• Confusion

  This case demonstrates the importance of including syphilis in a confusion screen as this patient was diagnosed following a low clinical suspicion. [ncbi.nlm.nih.gov]

  Symptoms of neurosyphilis usually include: Personality changes, such as confusion and irritability. Hearing loss. Vision problems. Decreased ability to concentrate. Memory loss. Difficulty speaking or understanding speech. [cigna.com]

• Personality Change

  Collateral history confirmed that these personality changes had been developing over the course of the previous 2 years. [ncbi.nlm.nih.gov]

  Symptoms of neurosyphilis usually include: Personality changes, such as confusion and irritability. Hearing loss. Vision problems. Decreased ability to concentrate. Memory loss. Difficulty speaking or understanding speech. [cigna.com]

• Tremor

  Tremor of the fingers and lips. Mild headaches. Disorderly appearance. Other symptoms may include: A wide gait. Numbness or tingling of the hands or feet. Muscle pain. Joint destruction because of lack of sensation (Charcot's joint). [cigna.com]

  Vibration and proprioception were decreased in both feet, and there was a fine intention tremor in both hands. Finger-to-nose movement was coarse because of the tremor. The patient’s gait was unsteady but was neither broad-based nor shuffling. [cmaj.ca]

  […] gait), or unable to walk Numbness in the toes, feet, or legs Problems with thinking, such as confusion or poor concentration Mental problems, such as depression or irritability Headache, seizures, or stiff neck Loss of bladder control (incontinence) Tremors [account.allinahealth.org]

An accurate diagnosis for syphilis is a complicated, multifactorial procedure. Lesions suspected to be of the syphilitic type are closely examined and biopsied, in order to confirm the presence of Tr. pallidum in the serous collected from these lesions. Dark field microscopy and direct immunofluorescence staining are methods that are generally applied for the detection of the pathogen in an active lesion. Amongst the indirect methods, the VDRL (venereal disease research laboratory) technique is used to screen for syphilis, while maintaining a markedly high number of false positive results. VDRL and RPR (rapid plasma reagin) are tests that detect antibodies that are not specific to syphilis.

The cerebrospinal fluid can also be tested in order to detect various markers suggestive of neurosyphilis. It is believed that an amount of cells > 20 cells/μL or more, a positive VDRL cerebrospinal fluid result and an elevated concentration of proteins strongly indicate neurosyphilis [21]. In fact, patients are assessed in terms of a CSF evaluation once a year, if their disease has been active for more than a year or if the course is of unclear duration.

Abnormal findings may also be detected via a magnetic resonance imaging of the head and are associated with neurologic complications. Ischemic indications, lesions of the cranial nerves and an atrophic spinal cords are amongst the most common abnormalities observed.

Lastly, electrophysiology can assist in the detection of tabetic syphilis (tabes dorsalis). Reflexes are poor or absent and the evoked potentials of the tibial nerve seem significantly delayed. Posterior tibial somatosensory evoked potentials are considered the most effective modality to diagnose meningeal syphilis that is still asymptomatic.

• Streptococcus Pneumoniae

  pneumoniae n = 4, Neisseria meningitidis n = 1). [journals.plos.org]

Management of neurosyphilis is primarily focused on attaining the treponemicidal levels of penicillin (PCN) in the cerebrospinal fluid, since the pathogen is very vulnerable to the antibiotic. However, the extent of therapy effectiveness is influenced by the associated involvement of the central nerve system and HIV infection.

Patients with latent/asymptomatic neurosyphilis (HIV negative individuals) may be treated with benzathine penicillin, which is administered intramuscularly over the course of 3 weeks. An alternative therapeutic scheme includes the intramuscular administration of aqueous benzylpenicillin G or procaine penicillin G for 2 weeks.

Patients with symptomatic neurosyphilis or those with asymptomatic neurosyphilis and a positive HIV test result may be treated with aqueous penicillin G, which is administered intravenously at 4-hour intervals or continuously for approximately 2 weeks. Procaine penicillin G and probenecid can be used per os for 2 weeks as well. Contraindications for the use of probenecid is prior known hypersensitivity to antibiotics of the sulfonamides group.

In the case of patients with an HIV infection and concomitant neurosyphilis, Treponema pallidum cannot be eradicated, as the effectiveness of penicillin is dramatically low. Patients tend to relapse and olanzapine can be administered in the sense of a supportive measure, should a patient present with syphilis-induced psychosis [22]. Cerebral gummata are usually treated with corticosteroids, alongside IV penicillin [23] and tabetic syphilis that has spread to the internal organs can be treated with gabapentin, according to some studies [24].

The long term outcome of patients with recognized T. pallidum but unremarkable cerebrospinal fluid is not clearly established at this time. Generally, in the majority of the patients, T. pallidum is eradicated from the central nervous system. Neurogenic complications and abnormalities may manifest when the immune system fails to clear T. pallidum.

Syphilis is caused by a Treponema pallidum infection; it belongs to a subgroup of Spirochaetales, from the family of Spirochaetaceae, genus Treponema. The subgroup itself encompasses 4 human infectious agents and six or more human non-infectious agents. The microorganism is T. pallidum subsp. pallidum that leads to venereal syphilis.

The yearly incidence rate in the USA revealed a significant increase: numbers where shown to have augmented 5 times from 1956 to 1990. Syphilis seems to be increasing in numbers amongst heterosexual, underprivileged individuals of the African ethnic group, or city inhabitants of large urban centers. According to the Center for Disease Control and Prevention, a complete picture of the infection's true dimensions is not yet possible, because patients very often do not report the disease [3] [4]. Men are more frequently affected than women.

Additionally, syphilis is often diagnosed in patients infected with HIV as well; the two conditions frequently exist as comorbidities. Such simultaneously active infections are commonly observed in African populations living in Africa and are attributed to a low health maintenance ability, poor services and information [5].

An individual contracts syphilis through sexual intercourse with another person. It is an infection that spreads to the central nervous system and chronic in nature. Symptomatology varies: many different organs may be damaged by the Treponema pallidum infection, but the disease may subside for a long period of time following an intensely active phase.

The Treponema species belongs to the group of the thin, helically spiraled organisms called spirochetes [6]. They are extremely sensitive to soap, water, drying and a temperature greater than 42°C; in any of these circumstances they can be eradicated.

The organism T. pallidum penetrates the body through tiny abrasions of the cutaneous or mucous membranes. Its adhesion to the host's cells causes the accumulation of mucopolysaccharidase. Obliterative endarteritis of the distal arterioles, inflammation and necrosis are three of the most predominant pathophysiological alterations. Immunity to re-infection occurs.

Meningovascular syphilis features endarteritis and perivascular inflammation. This results in the propagation of fibroblasts in the tunica intima, thinning of the tunica media, and inflammatory fibrosis of the tunica adventitia. Aneurysmal dilatation seldom occurs. Stenosis of the lumen increases the risk to cerebrovascular thrombosis, vascular occlusion and ischemia. Meningovascular syphilis is usually diagnosed within the first seven years following the primary infection.

General paresis constitutes a result of the vascular and ependymal inflammation, the fibrosis that the meninges sustain, the degenerative cortical parenchyma and the invasion of various organs by Treponema pallidum [7]. Progressed disease leads to the formation of Fisher plaques, namely restricted lesions in the brain with an absence of myelin, found mainly in the cortices of frontal and parietal lobes [8].

Public awareness is the most effective way to prevent the disease. Educational programs and identifying high-risk individuals would somehow limit the infection's incidence. Epidemiologic evaluation and preventive treatment of sexual contacts are essential.

Syphilis is classified as a sexually transmitted disease (STD) induced by Treponema pallidum, a spirochete bacterium, which can only infect humans. Following the incident of the initial infection with Treponema pallidum, the bacterium starts to proliferate within days and invades the CNS.

The disease leads to a plethora of clinical symptoms, such as:

• Acute meningeal syphilis
• Asymptomatic neurosyphilis
• General paresis
• Meningovascular syphilis
• Tabetic neurosyphilis

Although the exact incidence of neurosyphilis has not been accurately established, the infection seems to be particularly prevalent amongst the HIV positive population. During the last 15 years, it has also exhibited a marked rise in frequency, particularly in urban areas [1] [2]; women and newborns seem to be more commonly affected in the present, when compared to the past decades.

Neurosyphilis is an infection of the brain or spinal cord, caused by bacteria. Most often, individuals with chronic and untreated syphilis develop this disease.

Treponema pallidum is the primary etiologic agent in neurosyphilis. The development of neurosyphilis has been associated with a prior history of a Treponema pallidum infection, although not all patients develop this complication. There are different types of neurosyphilis, with the most common being asymptomatic neurosyphilis. Generally, the predominant symptoms are related with the central nervous system: patients may present with abnormal gait or inability to walk, numbness in the lower extremities, cognitive problems, mental illness, headaches, involuntary muscle contractions (i.e. seizures), bowel and bladder incontinence, tremors, and/or visual impairment. Others may be asymptomatic. Penicillin is the treatment of choice and patients recover fully if the infection is diagnosed and treated early.

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