Neurosyphilis

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Neurosyphilis

• Ryan Sanford
• 8.19.08

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A few facts

• 1900 syphilis was 1 cause of CV and
  neurological disease among middle aged persons
• Famous Persons who succumbed
• Al Capone
• King Edward VI
• Henri de Toulouse-Lautrec
• Suspected
• Adolf Hitler
• King Henry VIII
• Ivan the Terrible
• Vladimir Lenin
• Friedrich Nietzsche
• Vincent Van Gogh
• Robert Schumann

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And a poem
There was a young man from Back Bay Who thought
syphilis just went away He believed that a
chancre Was only a canker That healed in a week
and a day. But now he has acne vulgaris- (Or
whatever they call it in Paris) On his skin it
has spread From his feet to his head, And his
friends want to know where his hair is. Theres
more to his terrible plight His pupils wont
close in the light His heart is cavorting, His
wife is aborting, And he squints through his
gunbarrel sight. Arthralgia cuts into his
slumber His aorta is in need of a plumber But
now he has tabes, And sabershinned babies,
While of gummas he has quite a number. Hes
been treated in every known way, But his
spirochetes grow day by day Hes developed
paresis, Has long talks with Jesus, And thinks
hes the Queen of the May.
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Stages

• 1 Syphilis indurated, nontender ulcerative
  lesion accompanied by nontender, nonsuppurative
  regional LAN
• 2 Syphilis spirochetemia fever, malaise,
  diffuse LAN patchy alopecia HA hyperpgimented
  maculopapular rash on palms/soles
• Latent Syphilis recognized only by reactivity on
  serologic testing no clinical findings variable
  course
• 3 Syphilis neurosyphiliis, CV, gummatous
  pathophysiology is mainly endarteritis

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Natural History of Untreated Syphilis in
Immunocompetent Individuals
Golden, M. R. et al. JAMA 20032901510-1514.
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Palmar Lesions of 2 Syphilis
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3 Syphilis

• neurosyphilis to be discussed below
• CV syphilis
• endarteritis of vasavasorum ? progressive
  necrosis and loss of elastic tissue ? dilatation
  ? aneurysm
• esp of aortic arch and proximal thoracic aorta
  rarely dissect
• cause symptoms by encroachment/erode chest wall,
  SVC, recurrent laryngeal nerve, trachea and
  bronchi
• Gummatous syphilis indolent, destructive
  granulomatous lesions of soft tissue/bone
  ?scarring and disfigurement BENIGN??

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Obliterative Endarteritis
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Gummas
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So How to Dx?

• Exams of the lesions/chancre
• ulcer itself not adequate
• Dark field microscopy of exudate
• Corkscrew morphology
• Time and Tx sensitive
• Direct flourescent Ab DFA-TB applied to exudate
• Serology 2 stages
• Non Treponemal Serolgoic Tests VDRL, RPR, etc.
• Quantitative results 2/2 dilution
• Need fourfold decrease for clinical significance
• Treponemal Specific Tests not quantitative
• FTA-ABS (fluorescent treponemal antibody
  absorption)
• TP-PA (T. pallidum particle agglutination

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Tests per Stage

• 1 think lesion, serologies getting started
• Dark Field Microscopy or DFA-TP of exudate
• NTSTs less sensitive, must become positive, 2
  weeks
• TSTs can be positive before NTSTs
• 2 Serology best
• Microscopy of limited beneft
• FNs remote, but can have prozone effect 2/2 very
  high concenrations of Ab
• Latent
• NTSTs titers decrease
• TSTs remain positive
• 3 in general NTSTs can be nonreactive and TSTs
  reactive

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Diagnostic Studies in Neurosyphilis

• Serologies
• TSTs (i.e. FTA-ABS or TP-PA) almost always
  positive
• NSTS (i.e. RPR, VDRL) nonreactive in 25-30

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The Importance of the CSF

• Gold Standard
• Should be performed on any patient with
• positive serologies AND
• neurologic, ophthamologic, otic, or psychiatric
  symptoms
• Tests Must Include
• CSF-VDRL by itself diagnostic, nonreactive in
  25-30 of cases
• Cell Count pleocytosis, lymphocyte predominance,
  lt200 cells
• Protein increased, not gt200

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Course of Neurosyphilis
Most patients with 1/2 disease with CNS
involvement have resolution of CNS disease
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Clinical Syndromes of Neurosyphilis

• Asymptomatic continuation of disease within
  CNS and absence of ANY CNS symptom
• Meningitis
• Meningovascular endarteritis with infarction
  same as any other CVA anywhere within CNS takes
  5-12 years at minimum
• Parenchymal direct invasion of CNS parenchyma
  pathology fibrosis and atrophy
• General paresis
• Tabes dorsalis

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Symptomatic Meningitis

• Typically w/in first year of infection
• HA, confusion, N/V, stiff neck
• Cranial neuropathies, esp II, VII, VIII
• Less likely is myelitis

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Meningovascular Syphilis

• Average presentation in 7 years, but can occur
  months after primary infection
• Infectious endarteritis of CNS vasculature
• Prodrome HA, dizzy, personality changes
  preceding stroke (2/2 meningitis?)
• Can affect any vessel, but MCA and branches most
  common
• Think of it in CVA with young person, STI
  exposures

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General Paresis . . . of the insane

• Aka
• General paralysis of the insane
• Paretic neurosyphilis
• Dementia paralytica
• A progressive dementing illness
• Early forgetful, personality change, judgement
  loss less often depression, mania, psychosis
• Exam dysarthria, facial/limb hypotonia,
  intention tremors of face, reflex abnormalities,
  Argyll-Robertson pupils (more likely in tabes
  dorsalis)

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Tabes Dorsalis

• A disease of posterior columns and dorsal roots
• Sx
• Ataxia
• Lancinating pains sudden, brief, severe stabs of
  pain affecting limbs/back/face lasting
  minutes/days
• Paresthesias
• Gastric crises recurrent attacks of severe
  epigastric pain, nausea, vomiting
• Pupillary irregularities ½ Argyll-Robertson
• Absent LE reflexes, impaired vibratory/position
  sense

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The Argyll Robertson Pupil

• Small, nonresponsive to light, contracts normally
  to accommodation and convergence, dilates
  imperfectly to mydriatics, does not dilate to
  painful stimuli

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Treatment

• Not based on RCTs, but clinical experience and
  predicted penetration into CSF
• PCN long preferred, dosing based on stage of
  disease
• Secondary choics tetracyclines, macrolides,
  ceftriaxone
• Fourfold decrease in NTST general measure of
  success

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Treatment of Neurosyphilis

• Typically improves/halts S/Sx
• No RCTs proving dosing superiority
• Success of treatment judged by resolution/stabiliz
  ation of S/Sx and normalization of CSF
  abnormalities

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References

• ACP Medicine 2006 Syphilis and Nonvenereal
  Treponematoses
• UpToDate Neurosyphilis
• Update on Syphilis JAMA 2003 290(11)
• Syphilis and HIV Infection An Update Clinical
  Infectious Diseases 2007441222-8
• Mandell, Bennett, Dolin Principles and
  Practice of Infectious Diseases, 6th ed.
  Treponema pallidum.