What is the most likely diagnosis for a 1.2–1.3 cm hyperintense lesion involving the midbrain and pons on MRI?

Differential Diagnosis of a 1.2–1.3 cm Hyperintense Lesion in the Midbrain and Pons

The most likely diagnosis for a solitary 1.2–1.3 cm hyperintense lesion spanning the midbrain and pons is a demyelinating lesion from multiple sclerosis, though Rosai-Dorfman-Destombes disease, tuberculoma, and brainstem glioma must be excluded based on clinical context, enhancement pattern, and additional imaging features.

Primary Diagnostic Considerations

Multiple Sclerosis (Most Common)

• Infratentorial demyelinating lesions are characteristic of MS, with pontine lesions typically contiguous with cisterns or involving the floor of the fourth ventricle, medial longitudinal fasciculus, pontine surface, and pontine trigeminal root entry zone 1
• Midbrain MS lesions characteristically locate in the cerebral peduncles and close to the periaqueductal grey matter 1
• MS lesions in the pons are usually located at the periphery rather than centrally, which distinguishes them from ischemic small-vessel disease that affects central pons symmetrically 1
• The size (1.2–1.3 cm) is compatible with MS, as lesions are ordinarily larger than 3 mm in cross section 1
• At least one infratentorial lesion is part of the McDonald diagnostic criteria for MS when combined with other characteristic features 1, 2

Rosai-Dorfman-Destombes Disease (RDD)

• Parenchymal brainstem and pontine lesions are frequently infratentorial in neurologic RDD, appearing as patchy enhancing lesions 1
• RDD typically presents as solitary extraaxial dural masses mimicking meningioma, but parenchymal brainstem involvement does occur 1
• This diagnosis should be considered if the patient lacks typical MS clinical features (young adult, relapsing-remitting course) and especially if there is no evidence of dissemination in space on brain MRI 1

Tuberculoma

• Pontine tuberculomas typically show ring enhancement with surrounding edema and can present with cranial nerve palsies affecting nerves V-VIII 3
• Consider this diagnosis in patients with systemic tuberculosis symptoms, endemic exposure, or immunocompromised status 3
• CSF may show lymphocytic pleocytosis, though bacteriological studies may be negative 3

Brainstem Glioma

• Pontine gliomas can mimic tuberculomas on imaging, but typically cause more central pontine involvement with mass effect 3
• This diagnosis is more common in children and typically presents with rapidly progressive symptoms 3

Critical Diagnostic Algorithm

Step 1: Assess Clinical Context

• Age 20-40 years with relapsing-remitting neurological symptoms strongly suggests MS 2, 4
• Look for prior episodes of optic neuritis, partial myelitis, brainstem syndromes, or sensory disturbances that resolved spontaneously 2, 4
• Cranial nerve palsies (especially horizontal gaze palsy) suggest pontine tuberculoma 3
• Rapidly progressive symptoms in a child suggest brainstem glioma 3

Step 2: Evaluate Complete Brain MRI

• Search for additional lesions in periventricular, juxtacortical, and other infratentorial regions to establish dissemination in space for MS 1, 2
• MS requires at least three of four criteria: one gadolinium-enhancing or nine T2-hyperintense lesions, at least one infratentorial lesion, at least one juxtacortical lesion, and at least three periventricular lesions 1
• Solitary lesion without other characteristic MS features should prompt consideration of RDD, tuberculoma, or neoplasm 1, 3

Step 3: Assess Enhancement Pattern

• Ring enhancement with surrounding edema suggests tuberculoma or RDD 1, 3
• Homogeneous enhancement suggests RDD mimicking meningioma (though this is more typical for extraaxial lesions) 1
• Patchy enhancement can occur in both MS and RDD 1

Step 4: Order Targeted Additional Studies

• Complete spinal cord MRI (cervical and thoracic) is essential to identify asymptomatic cord lesions that strengthen MS diagnosis 2, 4
• Lumbar puncture for oligoclonal bands and IgG index provides supportive evidence for MS 2
• Test for anti-aquaporin-4 (AQP4) and anti-MOG antibodies to exclude neuromyelitis optica spectrum disorder and MOG-antibody disease, which can present with brainstem lesions and require different treatment 2, 4
• Consider contrast-enhanced T1-weighted imaging if not already performed, as tuberculomas typically show ring enhancement 3

Red Flags Requiring Alternative Diagnosis

Neuromyelitis Optica Spectrum Disorder (NMOSD)

• Periaqueductal lesions around the cerebral aqueduct or area postrema lesions in the dorsal brainstem are highly specific for NMOSD 1
• These lesions may cause intractable vomiting and hiccoughs (area postrema syndrome) 1
• AQP4-IgG antibody testing is mandatory, as MS therapies can worsen NMOSD 2, 4

MOG-Antibody Disease

• Mesencephalic-diencephalic lesions are characteristic of anti-MOG syndrome 1
• Prominent middle and superior cerebellar peduncle involvement also suggests MOG-antibody disease 1

Ischemic Small-Vessel Disease

• Symmetric central pontine lesions along transverse pontine fibers indicate vascular disease rather than MS 1
• This pattern corresponds to vascular border zones supplied by penetrating arteries from the basilar and superior cerebellar arteries 1

Neuro-Behçet Disease

• Large ovoid lesions close to the floor of the fourth ventricle should raise suspicion for neuro-Behçet disease 1

Common Pitfalls to Avoid

• Do not diagnose MS based solely on MRI findings without at least one clinical event consistent with acute demyelination 2, 4
• Do not assume all brainstem hyperintense lesions are demyelinating—carefully evaluate for tuberculoma (ring enhancement, systemic TB), RDD (solitary mass without other lesions), or neoplasm 1, 3
• Do not skip antibody testing for AQP4 and MOG, as these conditions require different treatment and can be worsened by MS therapies 2, 4
• Do not start MS-specific therapy until NMOSD and MOG-antibody disease are definitively excluded 2, 4
• MRI alone cannot distinguish between these entities—clinical correlation, enhancement pattern, and serological testing are essential 1, 2, 3