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 . 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 . Meningitis attributed to neurosyphilis mostly takes place subsequent to lack of management and therapy of early syphilis  . 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  . 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 .
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 .
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 , 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 , which leads to panuveitis, retinitis, papillitis or vitreitis, practically affecting every structure of the eye  . Patients experience impaired vision and photophobia. These manifestations typically indicate progressed disease.
Entire Body System
“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 . [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]
He may develop headaches or pain in other parts of the body, loss of appetite, a feeling of malaise, and sometimes a fever. A rash may appear on some parts of the body, and there may be a loss of hair or swollen glands. [jlhede.wordpress.com]
Syphilis is characterized by the phases of infectious process: Primary syphilis: chancre at site of inoculation Secondary syphilis: fever, malaise, lymphadenopathy, rash Early latent (year) and late latent (decades) About 1/3 progress to tertiary syphilis [eyewiki.aao.org]
[…] mucous membranes: diffuse rash, condyloma latum, other lesions Renal system: glomerulonephritis, nephrotic syndrome Liver: hepatitis Central nervous system: headache, meningismus, cranial neuropathy, iritis and uveitis Constitutional symptoms: fever, malaise [aafp.org]
General finding 1) Malaise, appetite loss, hoarseness, mild weight loss, headache,myalgia, arthralgia and low-grade fever 2) Lymphadenopathy and spleen enlargement 3) Hepatitis, gastritis and periostitis 4) Eye involvement:uveitis, iridocyclitis, choroidoretinitis [web.sapmed.ac.jp]
Headache, sore throat, malaise, myalgia, arthralgia, nausea and vomiting have been reported. Hypertension and subsequent hypotension and vascular collapse, including fatalities, have occurred. [pharmaceutical-journal.com]
- Intravenous Drugs
Stroke can occur as a result of neurosyphilis in its meningovascular form, and the likelihood of this increases with HIV co-infection, especially in high-risk groups such as intravenous drug users and men who have sex with men. [ncbi.nlm.nih.gov]
However, syphilis can be passed from person to person through sharing needles between injecting intravenous drug users (IVDUs). [patient.info]
Effects of HIV infection on the serologic manifestations and response to treatment of syphilis in intravenous drug users. Ann Int Med 1993;118:350-5. 50. Hutchinson CM, Hook EW III, Sheperd M et al. [reducetheburden.org]
In contrast, the rise in intravenous drug abuse, oral contraceptives and promiscuity among youths have contributed to the rise of syphilis in younger patients. [priory.com]
- Muscular Atrophy
atrophy.8 Although literature tells us that the symptomatic presentation may occur years after infection, in our case the evolution of the disease was accelerated and there was skin, genital and severe neurological manifestations. [revistanefrologia.com]
This type of entity may be labeled as syphilitic amyotrophy.  Muscular atrophy in syphilis is due to a progressive degeneration of the anterior horn cells in the spinal cord and may result from any type, parenchymatous or meningovascular, of syphilis [neurologyindia.com]
- Numbness of the Feet
Numbness in toes, feet, or legs 10. Difficult concentration 11. Convulsions 12. Stiff neck 13. Vision Impaired 14. Feeling weak Blood tests can be done to detect substances produced by bacteria that causes syphilis. [arizanagallery.blogspot.com]
- Blurred Vision
The patient had experienced blurred vision in his left eye and was diagnosed with ocular neurosyphilis 10 days prior to the current presentation. He was treated with a 14-day course of high-dose intravenous penicillin and oral prednisone. [ncbi.nlm.nih.gov]
We report a case of a 43-year-old male who presented multiple times to the Midland Regional Hospital, Tullamore (MRHT), Offaly, Ireland, with recurrent dizziness, blurred vision, and lower limb weakness. [emjreviews.com]
vision, reduced colour perception, impaired acuity, visual dimming and photophobia (17 per cent) Urinary symptoms, for example, incontinence (17 per cent) Lightning pains in the larynx, abdomen and various organs (10 per cent) Headache (10 per cent) [pharmaceutical-journal.com]
Visual symptoms were reported as diplopia, blurred vision, flashes, or a subjective decrease in vision. [jcm.asm.org]
- 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 . 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]
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]
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]
- Urinary Incontinence
incontinence 4 many patients also have the classic Argyll Robertson pupil that responds to accommodation but not to light 4 occurs decades after infection, often as the final manifestation 3,4 CSF Characteristic lumbar puncture findings depend on the [radiopaedia.org]
He had developed urinary incontinence 3 weeks ago. The patient had no known history of substance abuse or chronic alcohol use. He was not on any medications. There was no personal or family history of psychiatric illness. [ncbi.nlm.nih.gov]
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]
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]
Headaches, insomnia or interrupted sleep, absentmindedness and a fluctuating temper may appear in the beginning. [symptoma.com]
Case Reports Case 1 : A 49-year-old man was brought with history of insomnia and gradual deterioration of behaviour, of 2 years duration. He became unusually euphoric and began to lose concentration in his work as a teacher. [ijdvl.com]
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]
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]
- Memory Impairment
It has been cited that the most common presenting feature was personality change; however, memory impairment, hostility, confusion, hallucination and delusions may also occur in neurosyphilis.  These presenting signs should prompt a screening RPR. [scielo.org.za]
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]
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]
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 . 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.
- Cerebrospinal Fluid Abnormality
A diagnosis of neurosyphilis should be considered in patients with serologic evidence of syphilis and one or more of the following cerebrospinal fluid abnormalities; mononuclear pleocytosis, elevated protein, increased immunoglobulin G, or the presence [omicsonline.org]
Normalization of serum rapid plasma regain titers predicts normalization of cerebrospinal fluid and clinical abnormalities after treatment of neurosyphilis. [link.springer.com]
fluid abnormalities characterized by higher than normal amounts of white blood cells or protein 8. [nature.com]
Cerebrospinal fluid abnormalities in patients with syphilis: association with clinical and laboratory features. J Infect Dis. 2004; 189 :369–79. [ PubMed ] 13. Hicks CB. Serologic testing for syphilis. 2006 Uptodate.com. 14. [ncbi.nlm.nih.gov]
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 . Cerebral gummata are usually treated with corticosteroids, alongside IV penicillin  and tabetic syphilis that has spread to the internal organs can be treated with gabapentin, according to some studies .
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  . 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 .
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 . 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 . 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 .
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  ; 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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