Natural history
Primary syphilis occurs within days of infection via direct inoculation of Treponema pallidum at cutaneous or mucous membrane sites. It is manifested by a syphilitic ulcer, the chancre. Without treatment, the chancre heals over 3 to 6 weeks.
Most patients then progress to the secondary stage, in which systemic spirochetemia is marked primarily by flulike symptoms. Untreated, secondary syphilis also resolves over weeks to months.
After a clinically silent latency period ranging from months to years in length, about one-third of patients with untreated latent syphilis go on to develop tertiary disease, which can present as neurosyphilis, cardiovascular syphilis, gummatous syphilis, or a combination of these.
Syndromes
Neurosyphilis can be subdivided into several syndromes occurring at different points in the natural history of untreated syphilis:
| CNS Syphilitic Stage | Pathology | Manifestations | Peak Incidence | Neuroimaging |
| Asymptomatic CNS involvement | ||||
| Abnormal CSF ( protein, WBC >5, VDRL) | Asymptomatic | Any time | ± Meningeal enhancement | |
| Syphilitic meningitis (luetic meningitis) | ||||
| Aseptic meningitis (CSF profile as above) | Intracranial pressure, cranial nerve palsies, seizures | 1–2 yrs postinfection | Meningeal enhancement | |
| Meningovascular syphilis | ||||
| Cerebrovascular | Endarteritis, ± infarcts | Sudden-onset focal-cerebral symptoms, seizures | 5–7 yrs postinfection | Infarcts (cortical, subcortical) |
| Spinal | Endarteritis, meningeal inflammation, myelomalacia | Paresthesias, weakness, atrophy,sensory loss | 5–7 yrs postinfection | N/A |
| Parenchymatous neurosyphilis | ||||
| Paretic | Meningoencephalitis | Neuropsychiatric symptoms; seizures | 10–20 yrs postinfection | Optic atrophy |
| Tabetic | Leptomeningitis; degeneration of posterior roots, dorsal funiculi, brain stem | Pain, paresthesias, ataxia, Argyll-Robertson pupil, − deep tendon reflexes, − proprioception | 10–20 yrs postinfection | N/A |
| Gummatous neurosyphilis | ||||
| Gummata formation | Signs secondary to gummata mass effects, seizures | Any time | Mass lesions | |
| CNS = central nervous system; CSF = cerebrospinal fluid; WBC = white blood cells; N/A = not available; + = increased; − = decreased; ± = with or without | ||||
As shown, seizures can occur in all clinically expressed stages of neurosyphilis. In syphilitic meningitis, given the nonfocal stimulus of diffuse meningeal inflammation, seizures tend to be generalized. General paresis (dementia paralytica) also tends to be a nonlocalizing syndrome, and complicating seizures tend to be generalized. In contrast, gummatous neurosyphilis presents with signs and symptoms secondary to mass lesions at gummata sites, so partial seizures with localizing quality are often seen.
Diagnosis
Diagnosis of CNS syphilitic involvement involves consideration of a constellation of lab tests within the context of a careful history and physical examination. Well-known serologic screening tests include VDRL and rapid plasma reagent; fluorescent treponemal antibody absorption enhances diagnostic specificity after positive screening test results (although fluorescent treponemal antibody absorption has low specificity of disease activity, remaining positive long after successful treatment). Diagnosis of neurosyphilis requires positive serology and reactive CSF–VDRL.
CSF pleocytosis is the best measure of disease activity. In an untreated patient, there should be 5 or more WBC/mm3. CSF protein is usually elevated, and CSF glucose can be mildly decreased. Also, nonspecifically, CSF gamma globulin can be increased, and oligoclonal bands can be present.
Treatment
Treatment in all stages is of course directed at the underlying spirochete:
| Stage | Treatment |
| Primary, secondary, or early latent | PCN G 2–4 million U i.m. (PCN-allergic: doxycycline, tetracycline) |
| Late latent or unknown duration | PCN G 2–4 million U i.m. q.wk. x 3wks (PCN-allergic: doxycycline, tetracycline) |
| Tertiary disease, except neurosyphilis | PCN G 2–4 million U i.m. q.wk. x 3wks (PCN-allergic: doxycycline, tetracycline) |
| Neurosyphilis | PCN G 2–4 million U i.v. q4h. x 14 days PCN G 2–4 million U i.m. q.d. probenecid 500 mg q.i.d. x 14 days (PCN-allergic: no alternative) |
| PCN = penicillin | |
There is no role for seizure prophylaxis in syphilis. Anticonvulsant treatment should be initiated only after seizure expression. When antiepileptic drugs are needed, the routine principles apply.
Seizure-producing gummas responding too slowly to penicillin can be treated with steroids.23