What are the next steps for a 22-year-old patient with left-sided numbness and a negative Magnetic Resonance Imaging (MRI) result?

Next Steps for 22-Year-Old with Left-Sided Numbness and Negative Brain MRI

The most critical next step is to obtain MRI of the entire spine with and without gadolinium contrast, as unilateral numbness with negative brain MRI may represent spinal cord pathology, peripheral nerve disease, or early demyelinating disease not yet visible on brain imaging. 1, 2, 3

Immediate Diagnostic Workup

Spinal Imaging - First Priority

• MRI of the entire cervical and thoracic spine with and without gadolinium is essential, as approximately 20 patients with suspected multiple sclerosis and minimal or no brain MRI abnormalities were found to have spinal cord lesions that established the diagnosis 3
• The MRI protocol should include T1-weighted sequences pre- and post-contrast, T2-weighted sequences, and fat-suppressed sequences to detect compressive myelopathy, demyelinating lesions, or intramedullary pathology 2
• Cervical spondylotic myelopathy can present with unilateral numbness mimicking peripheral nerve disease, and early recognition is critical to prevent progression 4

Lumbar Puncture - Second Priority

• CSF analysis should be performed if spinal MRI is negative or shows demyelinating lesions, including cell count with differential, protein, glucose, IgG index and synthesis rate, oligoclonal bands, and viral studies (HSV1/2 PCR, VZV PCR) 5
• CSF may be the only abnormality in early autoimmune encephalitis or demyelinating disease when brain MRI is negative 5
• A normal lumbar puncture makes inflammatory/infectious causes less likely but does not exclude structural lesions 2

Peripheral Nerve Evaluation - If Central Imaging Negative

• MR neurography of the affected extremity should be considered if both brain and spine MRI are negative, as high-resolution nerve imaging can demonstrate traumatic injury, entrapment, or tumorlike lesions causing sensory dysfunction 6, 7
• MR neurography can visualize complex nerve structures along their entire pathway and distinguish nerves from surrounding tissue in a noninvasive manner 7

Critical Clinical Assessments

Neurological Examination Details

• Assess for upper motor neuron signs including hyperreflexia, clonus, positive Hoffman sign, and Babinski sign, which indicate spinal cord involvement requiring urgent imaging 4
• Check for ascending pattern of symptoms, as this suggests spinal cord lesion rather than peripheral nerve disease 2
• Evaluate hand grip strength versus proximal strength, as preserved grip with proximal weakness suggests cervical cord involvement 2

Time-Sensitive Considerations

• Serial neurological examinations every 2-4 hours are necessary to detect progression, particularly if any motor weakness develops 2
• If compressive myelopathy is identified, neurosurgical consultation and decompression within 24-48 hours is critical for optimal recovery 2

Laboratory Studies to Consider

• Complete blood count with differential, ESR, and CRP to evaluate for infection or inflammation 2
• Vitamin B12 level, as deficiency can cause unilateral or bilateral numbness with negative initial imaging 2
• HIV testing, syphilis serology, and Lyme serology if risk factors are present 2
• Antithyroid antibodies and autoimmune panel if autoimmune encephalitis is suspected 5

Common Pitfalls to Avoid

• Do not assume peripheral nerve disease without excluding central causes first, as cervical myelopathy commonly mimics carpal tunnel syndrome and other peripheral neuropathies 4
• Do not delay spinal imaging based on a negative brain MRI, as 45% of patients with suspected multiple sclerosis and minimal brain abnormalities had diagnostic spinal cord lesions 3
• Do not withhold lumbar puncture if clinical suspicion remains high, even with negative brain and spine MRI, as CSF may be the only abnormality in early inflammatory disease 5

If All Imaging Remains Negative

• Consider repeat brain MRI with specific sequences for subtle lesions, as some pathologies may not be visible on initial imaging 8
• Electromyography and nerve conduction studies may help localize peripheral nerve pathology if MR neurography is unavailable 7
• Close clinical follow-up with repeat neurological examination in 2-4 weeks is essential, as some conditions evolve over time and become visible on subsequent imaging 3