Neurosyphilis natural history, complications and prognosis: Difference between revisions
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==Overview== | ==Overview== | ||
The [[Symptom|symptoms]] of | The [[Symptom|symptoms]] of neurosyphilis usually develop secondary to long-term untreated [[syphilis]], and include [[diplopia]], [[impaired vision|impaired vision,]] [[hearing loss]], [[hoarseness]], persistent headache, [[dizziness]], [[vertigo]], lightning pains, impaired [[sensation]] and [[proprioception]], [[hypesthesia|hypesthesias]], [[hemiparesis]], [[homonymous hemianopsia]], [[slurred speech]] and [[dysarthria]]. If left untreated, most patients with neurosyphilis may progress to develop [[paralysis]], [[dementia]], [[charcot joint|Charcot arthropathy]], [[stroke]] and [[blindness]]. Common complications of neurosyphilis include [[meningitis]], meningiovascular syphilis, [[Argyll-Robertson pupil]], [[stroke]], [[cranial nerves|cranial nerve]] [[neuropathy|neuropathies]], [[dementia]], [[paralysis]], [[charcot joint|Charcot arthropathy]] ([[Charcot joint]]) of the foot and [[sensory ataxia|sensory ataxic gait]]. | ||
==Natural History== | |||
Neurosyphilis is one of the | Neurosyphilis is one of the late manifestations of untreated [[syphilis]] disease. | ||
* Painless [[chancre]] appears 3-4 weeks after exposure. | * 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. | * [[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. | ** 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. | * 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. | * Approximately 25% of patients develop recurrent symptoms in one year.<ref name="pmid1195972">{{cite journal| author=Nadol JB| title=Hearing loss of acquired syphilis: diagnosis confirmed by incudectomy. | journal=Laryngoscope | year= 1975 | volume= 85 | issue= 11 pt 1 | pages= 1888-97 | pmid=1195972 | doi=10.1288/00005537-197511000-00012 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=1195972 }} </ref> | ||
* Approximately 35% of patients develop tertiary syphilis, which includes the following complications: | * Approximately 35% of patients develop tertiary [[syphilis]], which includes the following complications:<ref name="pmid655658">{{cite journal| author=Jordan K, Marino J, Damast M| title=Bilateral oculomotor paralysis due to neurosyphilis. | journal=Ann Neurol | year= 1978 | volume= 3 | issue= 1 | pages= 90-3 | pmid=655658 | doi=10.1002/ana.410030114 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=655658 }} </ref><ref name="pmid26075118">{{cite journal| author=Ahsan S, Burrascano J| title=Neurosyphilis: An Unresolved Case of Meningitis. | journal=Case Rep Infect Dis | year= 2015 | volume= 2015 | issue= | pages= 634259 | pmid=26075118 | doi=10.1155/2015/634259 | pmc=4446468 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=26075118 }} </ref><ref name="pmid16397078">{{cite journal| author=Smith GT, Goldmeier D, Migdal C| title=Neurosyphilis with optic neuritis: an update. | journal=Postgrad Med J | year= 2006 | volume= 82 | issue= 963 | pages= 36-9 | pmid=16397078 | doi=10.1136/pgmj.2004.020875 | pmc=2563717 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=16397078 }} </ref> | ||
** Cardiovascular involvement after 15-30 years (80-85% of patients) including [[aortic aneurysm]], [[aortic regurgitation]], [[angina]], and [[heart failure]] | ** 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]]<ref name="pmid1951814">{{cite journal| author=Thomas SB, Quinn SC| title=The Tuskegee Syphilis Study, 1932 to 1972: implications for HIV education and AIDS risk education programs in the black community. | journal=Am J Public Health | year= 1991 | volume= 81 | issue= 11 | pages= 1498-505 | pmid=1951814 | doi= | pmc=1405662 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=1951814 }} </ref><ref name="pmid13301322">{{cite journal| author=GJESTLAND T| title=The Oslo study of untreated syphilis; an epidemiologic investigation of the natural course of the syphilitic infection based upon a re-study of the Boeck-Bruusgaard material. | journal=Acta Derm Venereol Suppl (Stockh) | year= 1955 | volume= 35 | issue= Suppl 34 | pages= 3-368; Annex I-LVI | pmid=13301322 | doi= | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=13301322 }} </ref><ref name="pmid10194456">{{cite journal| author=Singh AE, Romanowski B| title=Syphilis: review with emphasis on clinical, epidemiologic, and some biologic features. | journal=Clin Microbiol Rev | year= 1999 | volume= 12 | issue= 2 | pages= 187-209 | pmid=10194456 | doi= | pmc=88914 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=10194456 }} </ref><ref name="pmid17235095">{{cite journal| author=French P| title=Syphilis. | journal=BMJ | year= 2007 | volume= 334 | issue= 7585 | pages= 143-7 | pmid=17235095 | doi=10.1136/bmj.39085.518148.BE | pmc=1779891 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=17235095 }} </ref> | ** [[Gummatous]] lesions involving skin, bone and joints, associated with significant [[morbidity]] and [[mortality]]<ref name="pmid1951814">{{cite journal| author=Thomas SB, Quinn SC| title=The Tuskegee Syphilis Study, 1932 to 1972: implications for HIV education and AIDS risk education programs in the black community. | journal=Am J Public Health | year= 1991 | volume= 81 | issue= 11 | pages= 1498-505 | pmid=1951814 | doi= | pmc=1405662 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=1951814 }} </ref><ref name="pmid13301322">{{cite journal| author=GJESTLAND T| title=The Oslo study of untreated syphilis; an epidemiologic investigation of the natural course of the syphilitic infection based upon a re-study of the Boeck-Bruusgaard material. | journal=Acta Derm Venereol Suppl (Stockh) | year= 1955 | volume= 35 | issue= Suppl 34 | pages= 3-368; Annex I-LVI | pmid=13301322 | doi= | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=13301322 }} </ref><ref name="pmid10194456">{{cite journal| author=Singh AE, Romanowski B| title=Syphilis: review with emphasis on clinical, epidemiologic, and some biologic features. | journal=Clin Microbiol Rev | year= 1999 | volume= 12 | issue= 2 | pages= 187-209 | pmid=10194456 | doi= | pmc=88914 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=10194456 }} </ref><ref name="pmid17235095">{{cite journal| author=French P| title=Syphilis. | journal=BMJ | year= 2007 | volume= 334 | issue= 7585 | pages= 143-7 | pmid=17235095 | doi=10.1136/bmj.39085.518148.BE | pmc=1779891 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=17235095 }} </ref><ref name="pmid24315656">{{cite journal| author=Klein TA, Ridley MB| title=An old flame reignites: vagal neuropathy secondary to neurosyphilis. | journal=J Voice | year= 2014 | volume= 28 | issue= 2 | pages= 255-7 | pmid=24315656 | doi=10.1016/j.jvoice.2013.08.018 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=24315656 }} </ref> | ||
* Neurologic infection in 10-15 years (5-10% of patients) including [[Cranial nerves|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|tabes dorsalis]] typically occurs 10 to 30 years after primary infection by [[Treponema pallidum|treponema pallidum.]]<ref name="pmid14749871">{{cite journal| author=Schöfer H| title=[Syphilis. Clinical aspects of Treponema pallidum infection]. | journal=Hautarzt | year= 2004 | volume= 55 | issue= 1 | pages= 112-9 | pmid=14749871 | doi=10.1007/s00105-003-0608-0 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=14749871 }} </ref> | |||
* If left untreated, most patients with neurosyphilis may progress to develop [[paralysis]], [[dementia]], charcot arthropathy, [[stroke]] and [[blindness]]. | |||
* | |||
* | |||
The symptoms of tabes dorsalis typically occurs 10 to 30 years after primary infection by [[Treponema pallidum|treponema pallidum.]]<ref name="pmid14749871">{{cite journal| author=Schöfer H| title=[Syphilis. Clinical aspects of Treponema pallidum infection]. | journal=Hautarzt | year= 2004 | volume= 55 | issue= 1 | pages= 112-9 | pmid=14749871 | doi=10.1007/s00105-003-0608-0 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=14749871 }} </ref> | |||
If left untreated, most patients with | |||
===Complications=== | ===Complications=== | ||
Common complications of neurosyphilis include: | |||
*[[Meningitis]]<ref name="pmid24365430">{{cite journal| author=Berger JR, Dean D| title=Neurosyphilis. | journal=Handb Clin Neurol | year= 2014 | volume= 121 | issue= | pages= 1461-72 | pmid=24365430 | doi=10.1016/B978-0-7020-4088-7.00098-5 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=24365430 }} </ref> | *[[Meningitis]]<ref name="pmid24365430">{{cite journal| author=Berger JR, Dean D| title=Neurosyphilis. | journal=Handb Clin Neurol | year= 2014 | volume= 121 | issue= | pages= 1461-72 | pmid=24365430 | doi=10.1016/B978-0-7020-4088-7.00098-5 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=24365430 }} </ref> | ||
*Meningiovascular syphilis<ref name="pmid3890813">{{cite journal| author=Simon RP| title=Neurosyphilis. | journal=Arch Neurol | year= 1985 | volume= 42 | issue= 6 | pages= 606-13 | pmid=3890813 | doi= | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=3890813 }} </ref><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=Ann Intern Med | year= 1988 | volume= 109 | issue= 11 | pages= 855-62 | pmid=3056164 | doi= | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=3056164 }} </ref> | *Meningiovascular syphilis<ref name="pmid3890813">{{cite journal| author=Simon RP| title=Neurosyphilis. | journal=Arch Neurol | year= 1985 | volume= 42 | issue= 6 | pages= 606-13 | pmid=3890813 | doi= | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=3890813 }} </ref><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=Ann Intern Med | year= 1988 | volume= 109 | issue= 11 | pages= 855-62 | pmid=3056164 | doi= | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=3056164 }} </ref><ref name="pmid19093312">{{cite journal| author=Loewenfeld IE| title=The Argyll Robertson pupil 1869-1969. A critical survey of the literature. | journal=Surv Ophthalmol | year= 1969 | volume= 14 | issue= 3 | pages= 199-299 | pmid=19093312 | doi= | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=19093312 }} </ref> | ||
*[[Stroke]]<ref name="pmid7340118">{{cite journal| author=Hotson JR| title=Modern neurosyphilis: a partially treated chronic meningitis. | journal=West J Med | year= 1981 | volume= 135 | issue= 3 | pages= 191-200 | pmid=7340118 | doi= | pmc=1273113 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=7340118 }} </ref> | *[[Stroke]]<ref name="pmid7340118">{{cite journal| author=Hotson JR| title=Modern neurosyphilis: a partially treated chronic meningitis. | journal=West J Med | year= 1981 | volume= 135 | issue= 3 | pages= 191-200 | pmid=7340118 | doi= | pmc=1273113 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=7340118 }} </ref> | ||
*[[Cranial nerves|Cranial nerve]] [[Neuropathy|neuropathies]] <ref name=syphilisCNS>Musher, Daniel M., Richard J. Hamill, and Robert E. Baughn. "Effect of human immunodeficiency virus (HIV) infection on the course of syphilis and on the response to treatment." Annals of Internal Medicine 113.11 (1990): 872-881.</ref> | *[[Cranial nerves|Cranial nerve]] [[Neuropathy|neuropathies]] <ref name="syphilisCNS">Musher, Daniel M., Richard J. Hamill, and Robert E. Baughn. "Effect of human immunodeficiency virus (HIV) infection on the course of syphilis and on the response to treatment." Annals of Internal Medicine 113.11 (1990): 872-881.</ref> | ||
*[[ | * [[Dementia]]<ref name="pmid19148316">{{cite journal| author=Tso MK, Koo K, Tso GY| title=Neurosyphilis in a non-HIV patient: more than a psychiatric concern. | journal=Mcgill J Med | year= 2008 | volume= 11 | issue= 2 | pages= 160-3 | pmid=19148316 | doi= | pmc=2582679 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=19148316 }} </ref> | ||
* [[Paralysis]]<ref name="pmid23919113">{{cite journal| author=Kaynak G, Birsel O, Güven MF, Oğüt T| title=An overview of the Charcot foot pathophysiology. | journal=Diabet Foot Ankle | year= 2013 | volume= 4 | issue= | pages= | pmid=23919113 | doi=10.3402/dfa.v4i0.21117 | pmc=3733015 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=23919113 }} </ref> | |||
===Prognosis=== | ===Prognosis=== | ||
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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]
Overview
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.
Natural History
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.
- 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.
Complications
Common complications of neurosyphilis include:
- Meningitis[11]
- Meningiovascular syphilis[12][13][14]
- Stroke[15]
- Cranial nerve neuropathies [16]
Prognosis
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.
References
- ↑ Nadol JB (1975). "Hearing loss of acquired syphilis: diagnosis confirmed by incudectomy". Laryngoscope. 85 (11 pt 1): 1888–97. doi:10.1288/00005537-197511000-00012. PMID 1195972.
- ↑ Jordan K, Marino J, Damast M (1978). "Bilateral oculomotor paralysis due to neurosyphilis". Ann Neurol. 3 (1): 90–3. doi:10.1002/ana.410030114. PMID 655658.
- ↑ Ahsan S, Burrascano J (2015). "Neurosyphilis: An Unresolved Case of Meningitis". Case Rep Infect Dis. 2015: 634259. doi:10.1155/2015/634259. PMC 4446468. PMID 26075118.
- ↑ Smith GT, Goldmeier D, Migdal C (2006). "Neurosyphilis with optic neuritis: an update". Postgrad Med J. 82 (963): 36–9. doi:10.1136/pgmj.2004.020875. PMC 2563717. PMID 16397078.
- ↑ 5.0 5.1 Thomas SB, Quinn SC (1991). "The Tuskegee Syphilis Study, 1932 to 1972: implications for HIV education and AIDS risk education programs in the black community". Am J Public Health. 81 (11): 1498–505. PMC 1405662. PMID 1951814.
- ↑ 6.0 6.1 GJESTLAND T (1955). "The Oslo study of untreated syphilis; an epidemiologic investigation of the natural course of the syphilitic infection based upon a re-study of the Boeck-Bruusgaard material". Acta Derm Venereol Suppl (Stockh). 35 (Suppl 34): 3–368, Annex I-LVI. PMID 13301322.
- ↑ 7.0 7.1 Singh AE, Romanowski B (1999). "Syphilis: review with emphasis on clinical, epidemiologic, and some biologic features". Clin Microbiol Rev. 12 (2): 187–209. PMC 88914. PMID 10194456.
- ↑ French P (2007). "Syphilis". BMJ. 334 (7585): 143–7. doi:10.1136/bmj.39085.518148.BE. PMC 1779891. PMID 17235095.
- ↑ Klein TA, Ridley MB (2014). "An old flame reignites: vagal neuropathy secondary to neurosyphilis". J Voice. 28 (2): 255–7. doi:10.1016/j.jvoice.2013.08.018. PMID 24315656.
- ↑ Schöfer H (2004). "[Syphilis. Clinical aspects of Treponema pallidum infection]". Hautarzt. 55 (1): 112–9. doi:10.1007/s00105-003-0608-0. PMID 14749871.
- ↑ Berger JR, Dean D (2014). "Neurosyphilis". Handb Clin Neurol. 121: 1461–72. doi:10.1016/B978-0-7020-4088-7.00098-5. PMID 24365430.
- ↑ Simon RP (1985). "Neurosyphilis". Arch Neurol. 42 (6): 606–13. PMID 3890813.
- ↑ Lukehart SA, Hook EW, Baker-Zander SA, Collier AC, Critchlow CW, Handsfield HH (1988). "Invasion of the central nervous system by Treponema pallidum: implications for diagnosis and treatment". Ann Intern Med. 109 (11): 855–62. PMID 3056164.
- ↑ Loewenfeld IE (1969). "The Argyll Robertson pupil 1869-1969. A critical survey of the literature". Surv Ophthalmol. 14 (3): 199–299. PMID 19093312.
- ↑ Hotson JR (1981). "Modern neurosyphilis: a partially treated chronic meningitis". West J Med. 135 (3): 191–200. PMC 1273113. PMID 7340118.
- ↑ Musher, Daniel M., Richard J. Hamill, and Robert E. Baughn. "Effect of human immunodeficiency virus (HIV) infection on the course of syphilis and on the response to treatment." Annals of Internal Medicine 113.11 (1990): 872-881.
- ↑ Tso MK, Koo K, Tso GY (2008). "Neurosyphilis in a non-HIV patient: more than a psychiatric concern". Mcgill J Med. 11 (2): 160–3. PMC 2582679. PMID 19148316.
- ↑ Kaynak G, Birsel O, Güven MF, Oğüt T (2013). "An overview of the Charcot foot pathophysiology". Diabet Foot Ankle. 4. doi:10.3402/dfa.v4i0.21117. PMC 3733015. PMID 23919113.