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General Paresis

Neurosyphilis is an infection caused by the Treponema pallidum pathogen, which affects the central nervous system.


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.

Recurrent Infection
  • A large proportion of our patients had recurrent infection in the central nervous system despite therapy for early syphilis that met or exceeded current recommendations.[doi.org]
  • 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[symptoma.com]
Disorganized Behavior
  • This case report describes a patient presenting with disorganized behavior and later diagnosed with dementia in which neurosyphilis was found causative. This is followed by a pragmatic review of the diagnosis and treatment options for neurosyphilis.[ncbi.nlm.nih.gov]
Suicidal Ideation
  • These events were captured by a surveillance camera on the bridge; an acquaintance reported that he had previous suicidal ideation.[ncbi.nlm.nih.gov]
  • 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]
  • A 39-year-old man presented with a 6-month history of progressive visual loss (20/25 RE, 20/1200 LE) and transient headaches. Fundus examination demonstrated a 1 vitritis, mild macular edema and large optic disc neovascularization in both eyes.[ncbi.nlm.nih.gov]
  • CASE: A 65-year-old female with a history of HIV was admitted with a three-day history of worsening headache, confusion, and lethargy. On examination she was awake but confused.[ncbi.nlm.nih.gov]
  • A 31-year-old African-American homosexual man presented with bilateral hearing loss, constant vertigo, intermittent horizontal diplopia, and bilateral facial droop, which was associated with occipital headache without fever.[ncbi.nlm.nih.gov]
  • Headaches, insomnia or interrupted sleep, absentmindedness and a fluctuating temper may appear in the beginning.[symptoma.com]
Memory Impairment
  • He attended the clinic because of progressive attention and memory impairments as well as apathy, anxiety and irritability reported by family members.[doi.org]
  • The onset of the memory impairments was slow, observed firstly by his wife, with affected short term memory and preserved long term memory.[tmj.ro]
  • The presentation of mesial temporal encephalitis (limbic encephalitis) with status epilepticus and memory impairment is reported.[emedicine.medscape.com]
  • Headaches, insomnia or interrupted sleep, absentmindedness and a fluctuating temper may appear in the beginning.[symptoma.com]
  • The symptoms appear from months to a decade after the primary infection and may include seizures, hemiplegia, insomnia, personality changes, and dementia.[ajnr.org]
  • His history revealed that he was a heavy drinker (for 30 years, approximately 10 beers per day), abstinent from five months, when he presented an insomnia which wasn’t treatable with any sleeping pills.[tmj.ro]
  • Insomnia may occur. Visual problems may develop, including the inability of pupils to react to the light. This, along other ocular pathology, can result in photophobia, dimming of vision, and squinting.[newrepublic.com]
  • A subacute encephalitic prodrome is present, with headaches, vertigo, insomnia, and psychological abnormalities (eg, personality change, emotional lability, insomnia, decreased memory), followed by a gradually progressive vascular syndrome.[emedicine.medscape.com]
  • Diagnosis of neurosyphilis should be suspected in the presence of a global cognitive impairment consisting in disorientation, amnesia and severe impairment of speech and judgement and psychiatric symptoms such as depression, mania and psychosis, with[ncbi.nlm.nih.gov]
  • View Article PubMed Google Scholar Denays R, Collier A, Rubinstein M, Atsama P: A 51-year-old woman with disorientation and amnesia. Lancet. 1999, 354: 1786-10.1016/S0140-6736(99)09151-5.[doi.org]
  • Neurosyphilis showing transient global amnesia-like attacks and magnetic resonance imaging abnormalities mainly in the limbic system.[ncbi.nlm.nih.gov]
  • His verbal communication was relatively spare; however he did have a mild anomia and poor categorical fluency. A severe dysexecutive syndrome was also documented (with notably poor coding test and letter fluency).[doi.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.


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].

Sex distribution
Age distribution


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:

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.

Patient Information

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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Last updated: 2019-07-11 22:10