Infectious Disease · Treponema pallidum infection

Neurosyphilis

USMLE2PANCE
7

Bets

The facts most likely to be tested

1

Tabes dorsalis presents as demyelination of the dorsal columns and dorsal nerve roots, leading to sensory ataxia, lancinating pains, and loss of proprioception.

Confidence:
2

Argyll Robertson pupils are pathognomonic for neurosyphilis, characterized by pupils that accommodate but do not react to light.

Confidence:
3

General paresis manifests as progressive dementia, personality changes, and psychiatric disturbances due to chronic meningoencephalitis.

Confidence:
4

Lumbar puncture with CSF-VDRL is the diagnostic test of choice for neurosyphilis, though it has low sensitivity and high specificity.

Confidence:
5

A reactive serum treponemal test (e.g., FTA-ABS) is required to screen for syphilis before confirming neurosyphilis with CSF analysis.

Confidence:
6

Intravenous aqueous crystalline penicillin G for 10–14 days is the first-line treatment for all stages of neurosyphilis.

Confidence:
7

Jarisch-Herxheimer reaction is an acute febrile response occurring within 24 hours of initiating antibiotic therapy due to the rapid lysis of spirochetes.

Confidence:

Vignette unlocked

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?

+Reveal answer

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 required to confirm the diagnosis and guide treatment.

Mo

Depth

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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

Requires CSF-VDRL (highly specific) and CSF pleocytosis (>5 WBC/µL).

Treatment

Aqueous crystalline penicillin G IV is the gold standard. Penicillin allergy requires desensitization.

Prognosis

Irreversible damage if untreated; CSF cell count normalization is the primary marker of treatment success.

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Epidemiology & Etiology

Neurosyphilis can occur at any stage of infection, though it is most common in the tertiary phase. 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 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. A reactive serum FTA-ABS is required for screening. 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; patients must undergo desensitization rather than using alternative antibiotics. Ceftriaxone is an inferior alternative for those who cannot be desensitized.

Prognosis

Treatment halts progression but rarely reverses established neurological deficits. Patients require repeat lumbar puncture every 6 months until the CSF cell count returns to normal. 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