What is the differential diagnosis for an ovoid focus of abnormal signal in the upper cervical cord at C1 on T2-weighted Magnetic Resonance Imaging (MRI)?

Differential Diagnosis of Ovoid T2 Hyperintense Lesion at C1

The most critical differential diagnoses for a 6mm ovoid T2 hyperintense focus in the upper cervical cord at C1 include demyelinating disease (particularly multiple sclerosis), spinal cord tumor (especially low-grade glioma), and less commonly, vascular malformation or inflammatory/infectious myelitis.

Primary Diagnostic Considerations

Demyelinating Disease (Multiple Sclerosis)

Multiple sclerosis is the leading consideration for a small, focal cervical cord lesion in the appropriate clinical context. 1

• MS cord lesions are characteristically small (at least 3mm), covering less than two vertebral segments and usually less than half of the cord area 1
• The 6mm height of this lesion fits the typical MS pattern of short segment involvement 1
• MS lesions are typically located peripherally in the lateral or dorsal columns, though they can affect central grey matter 1
• The ovoid morphology described is consistent with MS, which can present with ovoid-shaped lesions 1
• MS lesions should be focal with clearly demarcated borders, cigar-shaped on sagittal images, and wedge-shaped on axial images 1

Critical next steps to establish MS diagnosis:

• Obtain brain MRI to assess for dissemination in space (periventricular, juxtacortical, infratentorial lesions) 2
• Evaluate for additional spinal cord lesions throughout cervical and thoracic regions 2
• Assess clinical history for prior neurological episodes suggesting dissemination in time 2
• Consider lumbar puncture for oligoclonal bands if MRI criteria are borderline 2

Intramedullary Spinal Cord Tumor

Low-grade gliomas (particularly astrocytomas) must be excluded, as they can present with focal T2 hyperintensity and may be indistinguishable from demyelinating lesions on initial imaging. 3, 4, 5

• Spinal cord astrocytomas can present as focal intramedullary lesions mimicking MS 4, 6
• Tumors typically demonstrate more mass effect, cord expansion, and persistent or progressive enhancement patterns compared to MS lesions 3, 4
• The small size (6mm) and ovoid shape make tumor less likely but do not exclude it 3
• Contrast enhancement characteristics are critical: MS lesions enhance for 2-8 weeks with nodular or open-ring patterns, while tumors show persistent enhancement 1

Key distinguishing features requiring contrast administration:

• Obtain cervical spine MRI with gadolinium to assess enhancement pattern 3, 5
• Tumors may show heterogeneous signal on long spin-echo sequences 7
• Serial imaging over 3-6 months can distinguish tumor (progressive) from MS (fluctuating lesion burden) 3

Vascular Malformation

Arteriovenous malformation or cavernous malformation should be considered, particularly if there is any history of acute symptom onset or hemorrhage. 1

• Vascular malformations can present with T2 hyperintensity and spotted, tortuous enhancement patterns 1
• The small, focal nature makes this less likely unless there is associated hemosiderin deposition 1
• Look for flow voids on T2-weighted sequences or blooming artifact on gradient-echo sequences to suggest vascular etiology 1

Inflammatory/Infectious Myelitis

Neuromyelitis optica spectrum disorder (NMOSD) is less likely given the short segment involvement but must be excluded. 1, 2

• NMOSD typically presents with longitudinally extensive transverse myelitis (LETM) affecting more than three vertebral segments 1
• The 6mm (short segment) lesion makes NMOSD unlikely, but anti-AQP4 antibody testing should be performed if clinical suspicion exists 2
• MOG-antibody disease can present with shorter cord lesions and should be tested if demyelination is suspected 2
• Neuro-sarcoidosis presents with longitudinally extensive lesions with leptomeningeal enhancement, not consistent with this presentation 1

Associated Syrinx Formation

If syringomyelia is present in association with this lesion, demyelinating disease becomes a critical consideration, though this association is rare. 3, 5

• Syrinx formation with demyelinating disease has been reported but is uncommon 3, 5
• Tumors (particularly astrocytomas) more commonly present with associated syrinx formation 7, 5
• Radiation necrosis can cause syrinx formation but requires prior radiation history 6
• The presence of syrinx should prompt biopsy consideration if imaging and clinical features remain ambiguous 5

Critical Diagnostic Algorithm

Step 1: Obtain MRI with gadolinium contrast

• Assess enhancement pattern (nodular/ring vs. heterogeneous/persistent) 1, 3
• Evaluate for additional brain and spinal cord lesions 2
• Include gradient-echo sequences to assess for hemorrhage or vascular malformation 1

Step 2: Clinical correlation

• Detailed history for prior neurological episodes (MS) vs. progressive symptoms (tumor) 2, 3
• Age consideration: MS typically presents in younger adults, though late-onset MS occurs 3

Step 3: Laboratory evaluation

• Lumbar puncture for oligoclonal bands and IgG index if MS suspected 2
• Anti-AQP4 and anti-MOG antibody testing to exclude NMOSD and MOG-antibody disease 2

Step 4: Serial imaging

• Repeat MRI in 3-6 months to assess for new lesions (MS) vs. progressive enlargement (tumor) 3
• If lesion remains stable and no additional lesions develop, consider biopsy 3, 5

Step 5: Biopsy consideration

• Reserve biopsy for cases where imaging and clinical features remain ambiguous after serial follow-up, or if tumor cannot be excluded 3, 5
• Recognize that even histopathology can be challenging, as demyelinating lesions may show reactive gliosis mimicking tumor 3

Common Pitfalls to Avoid

• Do not diagnose MS based solely on a single spinal cord lesion without demonstrating dissemination in space and time 2
• Do not assume all small cord lesions are MS; tumors can present identically and require different management 3, 4, 5
• Do not skip antibody testing for AQP4 and MOG, as misdiagnosis can lead to inappropriate MS therapy that worsens NMOSD 2
• Do not rely on absence of oligoclonal bands to exclude MS; seronegative MS exists 3
• Do not proceed directly to biopsy without contrast-enhanced imaging and clinical correlation 3, 5