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'''For patient information on Neurosyphilis, click [[Neurosyphilis (patient information)|here]]'''
__NOTOC__
 
<br />
{{DiseaseDisorder infobox |
{{DiseaseDisorder infobox |
   Name          = Syphilis |
   Name          = Syphilis |
   Image          = Treponema pallidum.jpg |
   Image          = Treponema pallidum.jpg |
   Caption        = Image of spiral-shaped organisms responsible for causing syphilis |
   Caption        = Image of spiral-shaped organisms responsible for causing syphilis |
  ICD10          = {{ICD10|A|50||a|50}}-{{ICD10|A|53||a|50}} |
  ICD9          = {{ICD9|090}}-{{ICD9|097}} |
  ICDO          = |
  OMIM          = |
  DiseasesDB    = |
  MedlinePlus    = 001327 |
  eMedicineSubj  =|
  eMedicineTopic = |
  eMedicine_mult =
}}
}}
{{Syphilis}}
{{Neurosyphilis}}
{{CMG}}; {{AOEIC}} {{LG}}
{{CMG}}; {{AE}}{{MMJ}}
 
==Overview==
*Neurosyphilis refers to a site of infection involving the [[central nervous system]] (CNS).
 
*Neurosyphilis 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 drug|antiretroviral therapy]] in recent years has further complicated such characterization.
 
==Clinical presentation: Four clinical types==
*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.
 
=====1. Asymptomatic meningitis=====
*Asymptomatic neurosyphilis usually has no signs or symptoms and is diagnosed exclusively with the presence or absence of CSF abnormalities notably pleocytosis, elevated protein, decreased glucose.
 
=====2. Symptomatic meningitis=====
*develops within 6-months to several years of primary infection
*typical meningitis symptoms: [[headache]], [[nausea]], [[vomiting]], [[photophobia]]
*Acute syphilitic [[meningitis]] usually occurs within the first year of infection; 10% of cases are diagnosed at the time of the secondary rash.
*Patients present with headache, meningeal irritation, and [[cranial nerve]] abnormalities, especially the [[optic nerve]], [[facial nerve]], and the [[vestibulocochlear nerve]].
*Rarely, it affects the spine instead of the brain, causing focal muscle weakness or sensory loss.
 
=====3. Meningovascular syphilis=====
*Meningovascular syphilis occurs a few months to 10 years (average, 7 years) after the primary syphilis infection.
*Meningovascular syphilis can be associated with [[prodromal]] symptoms lasting weeks to months before focal deficits are identifiable.
 
*Prodromal symptoms include:
:*unilateral numbness,
:*[[paresthesia]]s,
:*upper or lower extremity weakness,
:*[[headache]],
:*[[vertigo (medical)|vertigo]],
:*[[insomnia]], and
:*psychiatric abnormalities such as personality changes.
 
*The focal deficits initially are intermittent or progress slowly over a few days.


*However, it can also present as an infectious [[arteritis]] and cause an [[ischemia|ischemic]] [[stroke]], an outcome more commonly seen in younger patients.
==[[Neurosyphilis overview|Overview]]==


*[[Angiography]] may be able to demonstrate areas of narrowing in the blood vessels or total occlusion.
==[[Neurosyphilis pathophysiology|Pathophysiology]]==


=====4. Parenchymatous neurosyphilis=====
==[[Neurosyphilis causes|Causes]]==
*develops 15-20 years after primary infection
*[[argyll robertson pupil]]: small irregular pupil
*clinical presents as '''[[general paresis]]''' or '''[[tabes dorsalis]]''' with resultant [[ataxia]]
:*General paresis<ref name=AMN>{{cite journal | author = Richard B. Jamess, MD, PhD | title = [http://www.health.am/sex/syphilis/ Syphilis- Sexually Transmitted Infections], 2006. | journal =Sexually transmitted diseases treatment guidelines | volume = | issue = | pages = | year = 2002}}</ref>, otherwise known as general paresis of the insane, is a severe manifestation of neurosyphilis.


:*It is a chronic [[dementia]] which ultimately results in death in as little as 2-3 years.
==[[Neurosyphilis differential diagnosis|Differentiating Neurosyphilis from other Diseases]]==


:*Patients generally have progressive personality changes, memory loss, and poor judgment.
==[[Neurosyphilis risk factors|Risk Factors]]==


:*More rarely, they can have [[psychosis]], [[clinical depression|depression]], or [[mania]].
==[[Neurosyphilis natural history, complications and prognosis|Natural History, Complications and Prognosis]]==
 
:*Imaging of the brain usually shows atrophy.


==Diagnosis==
==Diagnosis==
*Clinical signs of neurosyphilis (i.e., cranial nerve dysfunction, [[meningitis]], [[stroke]], [[altered mental status|acute or chronic altered mental status]], loss of vibration sense, and auditory or ophthalmic abnormalities) warrant further investigation and treatment for neurosyphilis.
*Approximately 35% to 40% of persons with secondary syphilis have [[asymptomatic]] [[central nervous system]] (CNS) involvement, as demonstrated by any of these on [[cerebrospinal fluid]] (CSF) examination:
:*An abnormal leukocyte cell count, protein level, or glucose level
:*Demonstrated reactivity to Venereal Disease Research Laboratory ([[VDRL]]) antibody test
*Laboratory testing is helpful in supporting the diagnosis of neurosyphilis; however, no single test can be used to diagnose neurosyphilis in all instances.
===CSF analysis===
*[[CSF analysis|Cerebrospinal fluid (CSF) abnormalities]] are common in persons with early syphilis.
*Diagnosed by finding '''''high numbers of [[leukocytes]]''''' in the CSF or abnormally '''''high protein''''' concentration in the setting of syphilis infection.


*[[VDRL]] in [[cerebrospinal fluid]] (CSF-VDRL), which is highly specific but insensitive, is the standard serologic test for CSF. Although some advocate using the [[FTA-ABS|FTA-ABS test]] to improve sensitivity.
[[Neurosyphilis history and symptoms|History and Symptoms]] | [[Neurosyphilis physical examination|Physical Examination]] | [[Neurosyphilis laboratory findings|Laboratory Findings]] | [[Neurosyphilis MRI|MRI]] | [[Neurosyphilis other imaging findings|Other Imaging Findings]] | [[Neurosyphilis other diagnostic studies|Other Diagnostic Studies]]


*When reactive in the absence of substantial contamination of CSF with blood, it is considered diagnostic of [[neurosyphilis]]; however in early syphilis, it can be of unknown prognostic significance.<ref name="pmid3056164">{{cite journal |author=Lukehart SA, Hook EW, Baker-Zander SA, Collier AC, Critchlow CW, Handsfield HH |title=Invasion of the central nervous system by Treponema pallidum: implications for diagnosis and treatment |journal=[[Annals of Internal Medicine]] |volume=109 |issue=11 |pages=855–62 |year=1988 |month=December |pmid=3056164 |doi= |url= |accessdate=2012-02-16}}</ref>
==Treatment==


*Most other tests are both insensitive and nonspecific and must be interpreted in relation to other test results and the clinical assessment. Therefore, the laboratory diagnosis of [[neurosyphilis]] usually depends on various combinations of reactive serologic test results, CSF cell count or protein, and a reactive CSF-VDRL with or without clinical manifestations.
[[Neurosyphilis medical therapy|Medical Therapy]] | [[Neurosyphilis primary prevention|Primary Prevention]] | [[Neurosyphilis secondary prevention|Secondary Prevention]] | [[Neurosyphilis cost-effectiveness of therapy|Cost-Effectiveness of Therapy]] | [[Neurosyphilis future or investigational therapies|Future or Investigational Therapies]]


===HIV Co-infection===
==Case Studies==
*There is anecdotal evidence that the incidence of neurosyphilis is higher in [[HIV|HIV patients]], and some have recommended that all HIV-positive patients with syphilis should have a [[lumbar puncture]] to look for asymptomatic [[neurosyphilis]].<ref>{{cite journal | author=Walter T, Lebouche B, Miailhes P, ''et al.'' | title=Symptomatic relapse of neurologic syphilis after benzathine penicillin G therapy for primary or secondary syphilis in HIV-infected patients | journal=Clin Infect Dis | year=2006 | volume=43 | issue=6 | pages=787-90 | id=PMID 16912958 }}</ref>
[[Neurosyphilis case study one|Case #1]]


*Among persons with HIV infection, the [[Lumbar puncture#Diagnostics|CSF leukocyte count]] usually is elevated (>5 white blood cell count [WBC]/mm3); using a higher cutoff (>20 WBC/ mm3) might improve the specificity of [[neurosyphilis]] diagnosis.<ref name="pmid14745693">{{cite journal |author=Marra CM, Maxwell CL, Smith SL, Lukehart SA, Rompalo AM, Eaton M, Stoner BP, Augenbraun M, Barker DE, Corbett JJ, Zajackowski M, Raines C, Nerad J, Kee R, Barnett SH |title=Cerebrospinal fluid abnormalities in patients with syphilis: association with clinical and laboratory features |journal=[[The Journal of Infectious Diseases]] |volume=189 |issue=3 |pages=369–76 |year=2004 |month=February |pmid=14745693 |doi=10.1086/381227 |url=http://www.jid.oxfordjournals.org/cgi/pmidlookup?view=long&pmid=14745693 |accessdate=2012-02-16}}</ref>
==Related Chapters==
 
*The [[VDRL|CSF-VDRL]] might be non-reactive even when [[neurosyphilis]] is present.
 
*Therefore, additional evaluation using [[FTA-ABS|FTA-ABS testing]] on CSF can be considered. The [[FTA-ABS|CSF FTA-ABS test]] is less specific for [[neurosyphilis]] than the [[VDRL|CSF-VDRL]] but is highly sensitive; [[neurosyphilis]] is highly unlikely with a negative [[FTA-ABS|CSF FTA-ABS test]].<ref name="pmid343742">{{cite journal |author=Jaffe HW, Larsen SA, Peters M, Jove DF, Lopez B, Schroeter AL |title=Tests for treponemal antibody in CSF |journal=[[Archives of Internal Medicine]] |volume=138 |issue=2 |pages=252–5 |year=1978 |month=February |pmid=343742 |doi= |url=http://archinte.ama-assn.org/cgi/pmidlookup?view=long&pmid=343742 |accessdate=2012-02-16}}</ref>
 
==Related chapters==
*[[Syphilis]]
*[[Syphilis]]
*[[Congenital syphilis]]
*[[Congenital syphilis]]


==Resources==
==External Links==
*[http://hivinsite.ucsf.edu/InSite?page=kb-05-01-04 UCSF HIV InSite Knowledge Base Chapter: Syphilis and HIV]
*[http://colman.net/eadv/index.html "A New Gold Standard For Syphilis?" Poster Presentation for European Academy of Dermatology and Venereology 2004 Spring Symposium]
*[http://www.stdhelp.org/about/syphilis.php Syphilis Pictures and Information]
*[http://medinfo.ufl.edu/other/histmed/clancy/ Kipkeepers, Pox and Gleet Vendors: A Rapid History of Syphilis]
*[http://www.poxhistory.com/ POX: Genius, Madness, and the Mysteries of Syphilis]
*[http://www.yourstdhelp.com/syphilis.html Syphilis Informational resource ]
*[http://www.pbs.org/wnet/secrets/case_syphilis/index.html Secrets of the Dead (PBS): The Syphilis Enigma]
*[http://www.cbc.ca/ideas/Aids Syphilis and AIDS: Lessons from history]
*[http://www.cdc.gov/std/Syphilis/STDFact-Syphilis.htm "Syphilis fact sheet" from the Center for Disease Control]
*[http://www.cdc.gov/std/Syphilis/STDFact-Syphilis.htm "Syphilis fact sheet" from the Center for Disease Control]
*[http://www.nobel.se/medicine/laureates/1927/wagner-jauregg-lecture.html The treatment of dementia paralytica by malaria inoculation (A Nobel Prize lecture, December 13, 1927)]
*[http://www.niaid.nih.gov/factsheets/stdsyph.htm National Institute of Allergy and Infectious Diseases Factsheet]
*[http://uk.reuters.com/article/oddlyEnoughNews/idUKN1443055520080115 New study blames Columbus for syphilis spread from Reuters  Jan 15, 2008]
==References==
{{reflist|2}}


{{Diseases of the skin and appendages by morphology}}
{{Diseases of the skin and appendages by morphology}}
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[[Category:Disease]]
[[Category:Disease]]
[[Category:Gynecology]]
[[Category:Gynecology]]
[[Category:Infectious disease]]


[[Category:Bacterial diseases]]
[[Category:Bacterial diseases]]
[[Category:Sexually transmitted diseases]]
[[Category:Sexually transmitted diseases]]

Latest revision as of 00:00, 18 September 2019


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