Neurosyphilis

Aka: Neurosyphilis, Tabes Dorsalis, Argyll-Robertson Pupil, Prostitute Pupil, Syphilitic Paresis, Dementia Paralytica, Meningovascular Syphilis, Ocular Syphilis, Otosyphilis

1. See Also
   1. Syphilis
   2. Tertiary Syphilis
2. Epidemiology
   1. Occurs in 10% of untreated Syphilis
3. Pathophysiology
   1. Meningovasculitis
   2. Degenerative parenchymal changes in any part of the CNS
4. Symptoms
   1. Slow mental deterioration
   2. Headaches
   3. Dizziness
   4. Personality change
5. Signs
   1. Altered Mental Status
   2. Cranial Nerve palsy
      1. Any ophthalmic or auditory symptoms in Syphilis should be treated as Neurosyphilis regardless of Lumbar Puncture results
   3. Tremor of lips, Tongue or hands
   4. Seizures
   5. Ataxia or impaired gait
   6. Aphasia
   7. Hyperreflexia
   8. Cognitive changes to progressive Dementia
   9. Argyll Robertson Pupil
      1. See Miosis
      2. Mnemonic (Prostitute's Pupil): Pupil accomodates but does not react
         1. Pupil constricts during accommodation, but does not constrict to light
      3. Due to Midbrain lesion (superior colliculus, pretectal region)
         1. Typically bilateral lesions resulting in small, irregular pupils
6. Types
   1. Asymptomatic (at onset of Neurosyphilis)
      1. Cerebrospinal Fluid positive VDRL (Meningitis)
      2. Argyll-Robertson Pupil (Prostitute Pupil) may be present
   2. Meningeal Neurosyphilis
      1. Intracranial Pressure increased
   3. Ocular Syphilis
      1. Iritis, Uveitis or chorioretinitis
      2. Painless Vision Loss
      3. Evaluate with a complete Cranial Nerve exam and a Slit Lamp exam by ophthalmology
   4. Otosyphilis
      1. Sudden onset Sensorineural Hearing Loss (endocochlear Syphilis)
      2. Vertigo (Vestibular Neuronitis due to Syphilis)
      3. Tinnitus
   5. Meningovascular Syphilis
      1. Begins 5 to 10 years after initial infection
      2. Acute or subacute Aseptic Meningitis
      3. Risk of Cerebrovascular Accident (multiple small infarctions) with variable distribution
   6. Tabes Dorsalis (Tabetic Neurosyphilis)
      1. Demyelination of Posterior Column dorsal roots and dorsal root ganglia
      2. Onset 20 to 30 years after initial infection
      3. Results in sensory Ataxia of the legs
      4. Lancinating pain and Paresthesias
      5. Urinary Overflow Incontinence
      6. Absent knee and ankle Deep Tendon Reflexes
      7. Proprioception loss
      8. Abnormal Romberg Test and Ataxia
      9. Progressive degeneration of spinal cord (posterior roots, Posterior Columns)
      10. Charcot's Joints
      11. Argyll-Robertson Pupil (Prostitute Pupil)
   7. Syphilitic Paresis (Dementia Paralytica, Paretic Neurosyphilis)
      1. Chronic meningoencephalitis
      2. Emotional lability and altered personality as well as affect
      3. Memory deficits
      4. Progressive Dementia
      5. Dysarthria and other speech changes
      6. Myoclonic Jerks
      7. Action Tremor
      8. Seizures
      9. Hyperreflexia
      10. Positive Babinski Reflex
      11. Evolves into Psychosis
      12. Argyll-Robertson Pupil (Prostitute Pupil) may be present
7. Labs: CSF Evaluation
   1. See Syphylis Testing
   2. Screening
      1. CSF VDRL (high Specificity)
      2. CSF white cell count >10/mm3
      3. CSF Protein >50 mg/dl
   3. Retesting if CSF VDRL negative
      1. Treponemal specific CSF tests (e.g. TPHA)
         1. High False Positive Rate
         2. Consider TPHA index (compares CSF to serum titer)
      2. Spirochete DNA PCR from CSF sample
         1. Higher Specificity than TPHA
         2. Not yet widely available
   4. Experimental markers
      1. B-Cell chemoattractant chemokinge (CXCL13 or CXC motif)
         1. Increased CSF concentrations may reliably predict Neurosyphilis
         2. Marra (2010) Sex Transm Dis 37(5):283-7 [PubMed]
8. Management
   1. See Syphilis
   2. Penicillin (with probenacid 500 mg orally four times daily for 10-14 days)
      1. Aqueous crystalline Penicillin G
         1. Dose: 3-4 MU IV every 4 hours for 10-14 days (18-24 MU daily)
         2. Alternative: 0.75 to 1 MU/hour continuous IV
      2. Procaine Penicillin G (only in compliant patients)
         1. Dose 2.4 MU IM once daily for 14 days
         2. Use with Probenecid 500 mg qid for 14 days
   3. Penicillin Allergy
      1. Desensitize and treat with Penicillin
      2. Ceftriaxone 2 g IM/IV qd for 14 days
   4. Repeat testing for Syphilis
      1. Repeat Syphilis Testing at 6 and 12 months
      2. Expect four fold reduction in titer after treatment
         1. Reevaluate and HIV Test if fails to have four fold drop in titer
9. References
   1. (2019) Sanford Guide, accessed on IOS 11/6/2019
   2. Green, Cohen, Billington (2016) Crit Dec Emerg Med 30(11): 4-10
   3. Ricco (2020) Am Fam Physician 102(2): 91-8 [PubMed]
   4. Workowski (2010) MMWR Recomm Rep 59(RR-12): 1-110 [PubMed]