What is the diagnosis and management of a hyperintense lesion at the centrum semiovale, internal capsule, and corticospinal tract at the C6 level?

Differential Diagnosis and Management of Hyperintense Lesions at Centrum Semiovale, Internal Capsule, and Corticospinal Tract at C6

The pattern of hyperintense lesions involving the centrum semiovale, internal capsule, and corticospinal tract extending to the cervical cord at C6 most strongly suggests demyelinating disease, particularly multiple sclerosis, though neuromyelitis optica spectrum disorder (NMOSD), progressive multifocal leukoencephalopathy (PML), and amyotrophic lateral sclerosis (ALS) must be excluded based on specific imaging characteristics and clinical context. 1

Primary Differential Diagnosis

Multiple Sclerosis (Most Likely)

This distribution pattern is highly characteristic of MS when lesions meet specific criteria:

• Periventricular/centrum semiovale lesions: Must be ovoid/round, ≥3 mm, asymmetrically distributed, and directly abutting the lateral ventricles without intervening white matter 1
• Internal capsule involvement: The corticospinal tract normally shows hyperintensity in the posterior limb of the internal capsule on T2/FLAIR sequences due to large axons with thick myelin sheaths 2
• Cervical cord lesion at C6: Should be focal, cigar-shaped on sagittal view, wedge-shaped on axial view, <2 vertebral segments in length, occupying <50% of cord cross-section, and located peripherally in lateral or posterior columns 1

Key diagnostic features supporting MS: 1

• Sharp lesion borders
• Perpendicular orientation to corpus callosum ("Dawson's fingers")
• Juxtacortical lesions involving U-fibers
• Homogeneous T2 hyperintensity
• Possible nodular or ring enhancement (acute lesions)
• No significant mass effect

Neuromyelitis Optica Spectrum Disorder (Critical to Exclude)

Red flags that would shift diagnosis to NMOSD: 1

• Spinal cord: Longitudinally extensive transverse myelitis (LETM) affecting ≥3 vertebral segments at C6 level
• Brain: Cloud-like, poorly marginated lesions in centrum semiovale; periependymal lesions surrounding lateral ventricles
• Internal capsule: Diencephalic involvement with bilateral hyperintense lesions
• Cloud-like enhancement pattern
• Marked T1 hypointensity in cord lesions

Progressive Multifocal Leukoencephalopathy

Consider PML if patient is immunocompromised (especially on natalizumab): 1

• Centrum semiovale: Large (>3 cm), diffuse lesions with subcortical location, irregular borders, ill-defined toward white matter
• Evolution: Progressive expansion over weeks without stabilization
• Enhancement: Less than 50% show patchy or punctate enhancement
• Key distinguishing features: No mass effect despite large size; punctate microcystic appearance on T2; hyperintense on DWI at leading edge 1

Amyotrophic Lateral Sclerosis

Consider if predominantly motor symptoms: 3, 2

• Internal capsule: Distinct (not mild) T2 FLAIR hyperintensity in posterior limb that progressively accentuates
• Centrum semiovale: Hyperintensity along entire corticospinal tract course
• Cervical cord: May show signal changes but typically less prominent than brain findings
• Decreased fractional anisotropy on DTI with progressive decline 3

Diagnostic Algorithm

Step 1: Lesion Characterization on MRI

Obtain complete neuraxis imaging: 1

• Brain MRI with gadolinium (T1, T2, FLAIR, DWI sequences)
• Cervical and thoracic spine MRI with gadolinium
• Count and measure all lesions systematically

Apply MS diagnostic criteria (requires 3 of 4): 1

1. One gadolinium-enhancing lesion OR nine T2 hyperintense lesions
2. At least one infratentorial lesion
3. At least one juxtacortical lesion
4. At least three periventricular lesions

Step 2: Assess Red Flags for Alternative Diagnoses

Immediately exclude MS if: 1

• Symmetric distribution of lesions (suggests leukodystrophy or small vessel disease)
• LETM ≥3 vertebral segments (NMOSD until proven otherwise)
• Periaqueductal or area postrema lesions (NMOSD)
• Lesions >3 cm with progressive expansion (PML)
• Leptomeningeal enhancement (neurosarcoidosis)
• Selective posterior/lateral column involvement in cord (subacute combined degeneration)

Step 3: Obtain Confirmatory Testing

Essential laboratory workup:

• CSF analysis: Oligoclonal bands (present in MS, absent in serum) and elevated IgG index 1
• Aquaporin-4 antibodies (positive in 70% of NMOSD) 1
• MOG antibodies (if NMOSD suspected but AQP4-negative) 1
• JCV DNA in CSF (if PML suspected) 1
• Vitamin B12, copper levels (if posterior column involvement) 1

Clinical correlation required:

• Onset: Acute (hours-days) favors MS; subacute (weeks) favors PML 1
• Symptoms: Hemiparesis, aphasia, seizures suggest PML; optic neuritis, myelopathy suggest MS 1
• Immunosuppression status: Critical for PML risk stratification 1

Step 4: Management Based on Final Diagnosis

If Multiple Sclerosis confirmed:

• Initiate disease-modifying therapy based on disease activity
• Consider high-dose corticosteroids for acute relapses
• Monitor with serial MRI every 6-12 months

If NMOSD confirmed:

• Avoid MS therapies (may worsen disease)
• Initiate immunosuppression (rituximab, eculizumab, or inebalizumab)
• Aggressive acute treatment with high-dose steroids and plasma exchange

If PML confirmed:

• Discontinue immunosuppression if possible 1
• Consider immune reconstitution strategies
• Monitor for IRIS (immune reconstitution inflammatory syndrome)

Critical Pitfalls to Avoid

Do not diagnose MS based solely on centrum semiovale and internal capsule lesions - the cervical cord lesion characteristics are crucial for differentiation. A lesion extending >2 vertebral segments at C6 mandates NMOSD workup regardless of brain findings. 1

Do not assume normal hyperintensity in posterior internal capsule is pathological - mild hyperintensity can be normal due to large myelinated fibers of the corticospinal tract; only distinct, progressive hyperintensity is concerning for pathology. 3, 2

Do not delay CSF analysis - oligoclonal bands provide critical specificity when imaging is equivocal, particularly in older patients where vascular lesions confound interpretation. 1

Do not miss PML in immunosuppressed patients - subacute progression without stabilization, even with typical MS-like distribution, requires JCV testing before initiating or continuing immunosuppression. 1