What is the differential diagnosis and next steps for a patient with subacute quadriparesis (quadriplegia), urinary incontinence, and normal lumbar puncture (LP) results?

Subacute Quadriparesis with Upper Motor Neuron Signs: Differential Diagnosis and Management

This patient requires urgent MRI of the entire spine with and without contrast to identify a compressive myelopathy, which is the most likely diagnosis given the subacute onset, ascending pattern, upper motor neuron signs (hyperreflexia, clonus, increased tone), and urinary incontinence.

Key Clinical Features Pointing to Myelopathy

This presentation has multiple "red flags" indicating spinal cord pathology:

• Ascending pattern (legs before arms) suggests a spinal cord lesion rather than peripheral nerve or neuromuscular junction disease 1
• Upper motor neuron signs (hyperreflexia 3+, ankle clonus, increased tone) definitively localize to the spinal cord
• Urinary incontinence indicates involvement of autonomic pathways in the spinal cord
• Preserved hand grip with proximal weakness suggests cervical cord involvement sparing distal motor neurons
• Normal lumbar puncture makes inflammatory/infectious causes less likely but does not exclude structural lesions 2

Primary Differential Diagnoses

1. Compressive Myelopathy (Most Likely)

• Epidural abscess - can present subacutely with ascending weakness and sphincter dysfunction
• Spinal cord tumor (intramedullary or extramedullary) - meningioma, ependymoma, astrocytoma
• Epidural hematoma - though typically more acute
• Herniated disc with cord compression - cervical level given arm involvement

2. Inflammatory/Demyelinating Myelopathy

• Transverse myelitis - though typically would show CSF abnormalities (elevated protein, pleocytosis) 2
• Multiple sclerosis - first presentation with longitudinally extensive transverse myelitis
• Neuromyelitis optica spectrum disorder - can have normal initial LP

3. Vascular Myelopathy

• Spinal cord infarction - though onset usually more acute
• Spinal arteriovenous malformation with venous congestion 3
• Anterior spinal artery syndrome - though typically causes dissociated sensory loss

4. Infectious Myelopathy

• Spinal epidural abscess - most urgent consideration
• Intramedullary abscess - rare but can occur 4

Immediate Diagnostic Workup

Urgent Neuroimaging (Within Hours)

MRI of the entire spine (cervical, thoracic, lumbar) with and without gadolinium contrast is the single most critical test 1. This protocol should include:

• T1-weighted sequences pre- and post-contrast to identify enhancement patterns
• T2-weighted sequences to assess cord signal abnormalities and edema
• Fat-suppressed sequences (STIR) to detect epidural collections or inflammation 2
• Sagittal and axial views at 3-4mm thickness 2

If MRI is contraindicated or unavailable within 24 hours, proceed with CT myelography 2, though this is suboptimal for intramedullary pathology.

Additional Laboratory Studies

Despite normal LP, obtain:

• Complete blood count with differential - leukocytosis suggests infection/abscess
• Erythrocyte sedimentation rate and C-reactive protein - elevated in infection or inflammation
• Blood cultures if febrile or suspicion for epidural abscess
• Vitamin B12 level - subacute combined degeneration (though sensory symptoms typically present)
• HIV testing, syphilis serology (RPR/VDRL), Lyme serology if risk factors present 2
• Aquaporin-4 antibodies if demyelinating disease suspected
• Thyroid function tests - thyroid myelopathy is rare but treatable

Repeat Lumbar Puncture Considerations

While the initial LP was normal, consider repeat LP if imaging is non-diagnostic 2:

• CSF can be initially normal in early viral encephalomyelitis and become abnormal 24-48 hours later 2
• Send CSF for: cell count, protein, glucose, oligoclonal bands, IgG index, cytology
• Consider viral PCR panel (HSV, VZV, enterovirus) and bacterial/fungal cultures

Critical Management Steps

Immediate Actions (Before Imaging Results)

• Neurosurgical consultation - compressive lesions may require emergency decompression
• Empiric antibiotics if any concern for epidural abscess (vancomycin + third-generation cephalosporin + metronidazole) - do NOT delay for imaging if patient is deteriorating
• High-dose corticosteroids (methylprednisolone 1g IV daily) can be considered if transverse myelitis is suspected, but ideally after imaging to avoid masking infection 1
• Respiratory monitoring - ascending myelopathy can progress to respiratory failure; check vital capacity and negative inspiratory force

Monitoring for Deterioration

• Serial neurological examinations every 2-4 hours to detect progression
• Respiratory function - vital capacity <15 mL/kg or negative inspiratory force <-20 cm H₂O indicates need for ICU monitoring
• Bladder management - post-void residual; may need intermittent catheterization

Common Pitfalls to Avoid

1. Assuming normal LP excludes all spinal cord pathology - structural lesions (tumors, abscesses, vascular malformations) often have normal CSF 2, 1

2. Delaying imaging for additional laboratory tests - MRI spine is the definitive diagnostic test and should not be delayed 1

3. Mistaking this for Guillain-Barré syndrome - the presence of hyperreflexia, clonus, and increased tone definitively excludes GBS, which causes areflexia 5, 6

4. Focusing only on cervical spine imaging - obtain entire spine imaging as lesions can be at any level, and multiple levels may be involved 1

5. Administering steroids before ruling out infection - if epidural abscess is present, steroids without antibiotics can be catastrophic

Prognosis and Timing

Time is critical - compressive myelopathies causing progressive neurological deficits require decompression within 24-48 hours for optimal recovery 1, 4. Delays beyond this window significantly worsen functional outcomes and may result in permanent paralysis.