Neurosyphilis-associated longitudinally extensive transverse myelitis with severe bladder dysfunction and radiologic resolution: a case report

Technical Summary: Neurosyphilis-Associated Longitudinally Extensive Transverse Myelitis

Problem Statement
Longitudinally extensive transverse myelitis (LETM) is a radioclinical syndrome with a broad differential diagnosis, often immediately prompting suspicion of autoimmune etiologies such as aquaporin-4 (AQP4)-related neuromyelitis optica spectrum disorder (NMOSD) or myelin oligodendrocyte glycoprotein (MOG) antibody-associated disease. However, infectious causes, particularly neurosyphilis, remain clinically significant because they are potentially reversible if identified early. Neurosyphilis is a known "great mimicker" that can present with spinal cord involvement, including longitudinally extensive lesions, sensory disturbances, pyramidal signs, and sphincter dysfunction. The diagnostic challenge lies in distinguishing syphilitic myelitis from autoimmune inflammatory myelopathies, especially in human immunodeficiency virus (HIV)-negative patients without other overt infectious manifestations, where reliance on a single test is insufficient.

Methodology
This study presents a single case report of a 31-year-old HIV-negative male patient who presented with progressive thoracic myelopathy. The diagnostic approach followed a comprehensive integration of neurological findings, serology, cerebrospinal fluid (CSF) analysis, and imaging:

• Clinical Evaluation: The patient presented with a one-month history of progressive heat sensation, numbness, and hyperesthesia in the lower limbs, followed by proximal weakness, urinary retention, and stool incontinence. Neurological examination revealed bilateral pyramidal signs and upper motor neuron involvement.
• Imaging: Whole-spine magnetic resonance imaging (MRI) was performed to characterize the spinal cord lesion. Brain MRI was also conducted to rule out intracranial pathology.
• Serological and CSF Testing: The diagnostic workup included serum rapid plasma reagin (RPR), Treponema pallidum particle agglutination (TPPA), and CSF Venereal Disease Research Laboratory (VDRL) testing. Autoimmune markers, specifically AQP4 and MOG antibodies, were tested. Oligoclonal bands were assessed in both CSF and serum.
• Electrophysiology and Urodynamics: Nerve conduction studies, somatosensory evoked potentials, visual evoked potentials, and urodynamic studies were utilized to assess peripheral nerve function and bladder mechanics.
• Treatment Protocol: The patient received a 14-day course of intravenous ceftriaxone (2 g every 12 hours) for anti-treponemal therapy. Concurrently, due to the initial uncertainty regarding inflammatory myelitis, high-dose methylprednisolone pulse therapy was administered for five days, followed by an oral prednisolone taper.
• Longitudinal Follow-up: The patient was monitored for clinical recovery, repeat CSF analysis (specifically VDRL), and follow-up MRI to assess radiologic resolution over a period extending to one year post-discharge.

Key Results

• Diagnostic Findings: Serum RPR was reactive at 1:128, and TPPA was positive at 1:20480. CSF VDRL was reactive at 1:8. Crucially, AQP4 and MOG antibodies were negative, and oligoclonal bands were absent. HIV testing was negative. The initial CSF sample showed significant blood contamination (3840 RBCs/µL), which complicated the interpretation of the VDRL result according to standard guidelines, though the totality of evidence supported the diagnosis.
• Imaging: Initial MRI revealed diffuse T2 hyperintensity in the central spinal cord from T6 to T10, consistent with LETM, without cord enlargement or compressive lesions.
• Clinical Outcome: Following treatment, the patient's bladder function gradually recovered, with spontaneous voiding returning approximately 3.5 weeks after discharge. Stool incontinence improved after pulse therapy.
• Radiologic and Laboratory Resolution: Six months after treatment, follow-up MRI demonstrated complete resolution of the thoracic cord signal abnormality. Repeat CSF testing showed non-reactive VDRL results and normalized protein parameters.
• Long-term Status: At one-year follow-up, the patient retained only rare, intermittent limb twitching, with no significant residual neurological deficits.

Significance and Claims
The paper claims that neurosyphilis should be included in the differential diagnosis of LETM, particularly in patients presenting with prominent autonomic dysfunction (severe bladder and bowel issues) and negative AQP4/MOG antibodies. The authors emphasize that while the association between neurosyphilis and LETM is rare, it is a critical "reversible mimic" of autoimmune myelitis.

The significance of this case lies in its longitudinal documentation of a favorable outcome. Unlike many short-term reports, this case demonstrates:

1. Diagnostic Value: The utility of syphilis testing in atypical myelitis cases where autoimmune markers are negative.
2. Clinical Correlation: The recovery of bladder function serves as a meaningful clinical marker of neurological improvement, complementing radiologic findings.
3. Radiologic Resolution: The case provides evidence that spinal cord signal abnormalities in syphilitic myelitis can fully resolve with appropriate treatment.
4. Diagnostic Strategy: It reinforces the principle that LETM is a syndrome rather than a specific diagnosis. The authors argue that in patients with LETM and prominent sphincter dysfunction, syphilis testing should be incorporated early into the diagnostic evaluation rather than reserved as a late exclusion test.

The authors conclude that integrating serologic, CSF, imaging, and longitudinal follow-up data is essential for interpreting unusual presentations of myelitis and ensuring that treatable infectious causes are not overlooked.