Infectious Disease · Treponema pallidum infection
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Tabes dorsalis presents as demyelination of the dorsal columns and dorsal nerve roots, leading to sensory ataxia, lancinating pains, and loss of proprioception.
Argyll Robertson pupils are highly characteristic of neurosyphilis, characterized by pupils that accommodate but do not react to light.
General paresis manifests as progressive dementia, personality changes, and psychiatric disturbances due to chronic meningoencephalitis.
Lumbar puncture with CSF-VDRL is the diagnostic test of choice for neurosyphilis, though it has low sensitivity and high specificity.
A reactive serum nontreponemal test (e.g., RPR/VDRL) confirmed by a treponemal test (e.g., TP-PA or FTA-ABS) establishes systemic syphilis before confirming neurosyphilis with CSF analysis.
Intravenous aqueous crystalline penicillin G for 10–14 days is the first-line treatment for all stages of neurosyphilis.
Jarisch-Herxheimer reaction is an acute febrile response occurring within 24 hours of initiating antibiotic therapy due to the rapid lysis of spirochetes.
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A 58-year-old male presents to the clinic with a 6-month history of progressive gait instability and shooting pains in his legs. Physical examination reveals bilateral pupils that constrict with accommodation but fail to constrict to light. He has absent deep tendon reflexes in the lower extremities and impaired vibration and position sense in the feet. A serum RPR is reactive, and a confirmatory FTA-ABS is positive.
What is the most appropriate next step in the management of this patient?
Lumbar puncture for CSF-VDRL analysis
The patient's clinical presentation of tabes dorsalis and Argyll Robertson pupils is highly suggestive of neurosyphilis; therefore, a lumbar puncture is indicated to confirm the diagnosis and guide treatment.
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Etiology / Epidemiology
Caused by Treponema pallidum invasion of the CNS; occurs in patients with untreated syphilis and high-risk sexual behavior.
Clinical Manifestations
Presents as tabes dorsalis, Argyll Robertson pupils, or general paresis. Meningovascular or parenchymatous involvement.
Diagnosis
Supported by a reactive CSF-VDRL (highly specific but insensitive) and/or CSF pleocytosis (>5 WBC/µL).
Treatment
Aqueous crystalline penicillin G IV is the treatment of choice. Penicillin allergy generally warrants skin testing and desensitization; ceftriaxone is an alternative (CDC 2021).
Prognosis
Irreversible damage if untreated; Serum RPR response (CDC 2021) or CSF cell count normalization marks treatment success.
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Epidemiology & Etiology
Neurosyphilis can occur at any stage of infection; in the antibiotic era, early forms (syphilitic meningitis, ocular/otic syphilis, meningovascular disease) are more common than late parenchymatous forms (tabes dorsalis, general paresis). Patients with HIV coinfection are at significantly higher risk for rapid progression. It results from hematogenous spread of the spirochete to the CNS.
Pertinent Anatomy
Infection targets the meninges (meningovascular syphilis) and the dorsal columns of the spinal cord. Involvement of the midbrain tectum leads to the classic pupillary findings.
Pathophysiology
The spirochete induces an inflammatory response causing obliterative endarteritis of small vessels. This leads to ischemia and infarction of neural tissue. Chronic inflammation results in the demyelination of the posterior columns.
Clinical Manifestations
Argyll Robertson pupils (accommodate but do not react to light) are highly characteristic (though not pathognomonic). Tabes dorsalis presents with sensory ataxia and lancinating pains. General paresis manifests as progressive dementia and personality changes. Meningovascular forms present with acute stroke-like symptoms in young patients.
Diagnosis
Diagnosis is confirmed by a reactive CSF-VDRL test. Serologic evidence of syphilis precedes CSF testing: screen with a nontreponemal test (RPR/VDRL) confirmed by a treponemal test, or use the reverse algorithm (treponemal immunoassay first); TP-PA is the preferred manual treponemal test per CDC 2024. CSF pleocytosis (>5 WBC/µL) or elevated CSF protein (>45 mg/dL) supports the diagnosis.
Treatment
The treatment of choice is Aqueous crystalline penicillin G (18–24 million units/day IV). Penicillin allergy is a major barrier; confirm with skin testing and, if needed, pursue desensitization (CDC 2021); ceftriaxone 1–2 g daily for 10–14 days is an alternative supported by limited data.
Prognosis
Treatment halts progression but rarely reverses established neurological deficits. Repeat lumbar puncture is unnecessary for patients without HIV (or with HIV on ART) who show serologic and clinical responses (CDC 2021); otherwise, repeat CSF examination every 6 months until the cell count normalizes. Failure to normalize suggests treatment failure or HIV-related progression.
Differential Diagnosis
Multiple Sclerosis: optic neuritis and relapsing-remitting course
Lyme Disease: history of tick bite and erythema migrans
HIV-associated neurocognitive disorder: absence of reactive CSF-VDRL
B12 Deficiency: subacute combined degeneration with macrocytic anemia
Diabetes Mellitus: peripheral neuropathy without pupillary changes