Diagnostic Criteria and Imaging Features for Brainstem Hyperintense Lesions

Multiple Sclerosis (MS)

• Infratentorial demyelinating lesions are a hallmark of MS; pontine lesions typically abut the cisterns, involve the floor of the fourth ventricle, the medial longitudinal fasciculus, the pontine surface, or the trigeminal root entry zone【1】.
• Midbrain MS lesions most often involve the cerebral peduncles and are situated adjacent to the periaqueductal gray matter【1】.
• Pontine MS plaques are characteristically peripheral rather than centrally located, helping to differentiate them from the symmetric central pontine involvement seen in small‑vessel ischemic disease【1】.
• Lesions measuring 1.2–1.3 cm are compatible with MS, as typical demyelinating plaques exceed 3 mm in cross‑section【2】.
• The presence of at least one infratentorial lesion satisfies a component of the McDonald diagnostic criteria for MS when other characteristic features are also present【2】.
• MS diagnosis requires dissemination in space: at least three of four MRI criteria—(1) one gadolinium‑enhancing or ≥9 T2‑hyperintense lesions, (2) ≥1 infratentorial lesion, (3) ≥1 juxtacortical lesion, and (4) ≥3 periventricular lesions【2】.

Rosai‑Dorfman‑Destombes Disease (RDD)

• Parenchymal brainstem and pontine involvement in neurologic RDD frequently appears as infratentorial, patchy‑enhancing lesions on MRI【5】.
• RDD can mimic extra‑axial dural masses (meningioma‑like) when lesions are solitary and extra‑axial, but true parenchymal brainstem lesions also occur【5】.
• Ring enhancement with surrounding edema may be seen in RDD, overlapping with the appearance of tuberculoma【5】.
• Homogeneous enhancement is typical of extra‑axial RDD lesions that resemble meningioma【5】.
• When a solitary brainstem lesion lacks additional MS‑type disseminated lesions, RDD, tuberculoma, or neoplasm should be considered【5】.

Neuromyelitis Optica Spectrum Disorder (NMOSD)

• Periaqueductal lesions surrounding the cerebral aqueduct or area‑postrema lesions in the dorsal brainstem are highly specific for NMOSD【1】.
• Area‑postrema involvement can produce intractable vomiting and hiccups (area‑postrema syndrome)【1】.
• Testing for AQP4‑IgG antibodies is mandatory because conventional MS therapies may exacerbate NMOSD【4】.

Myelin Oligodendrocyte Glycoprotein (MOG)‑Antibody Disease

• Mesencephalic‑diencephalic lesions are characteristic of anti‑MOG syndrome【1】.
• Prominent involvement of the middle and superior cerebellar peduncles also points toward MOG‑antibody disease【1】.

Ischemic Small‑Vessel Disease

• Symmetric central pontine lesions aligned along the transverse pontine fibers indicate a vascular (small‑vessel) etiology rather than demyelination【1】.

Neuro‑Behçet Disease

• Large ovoid lesions adjacent to the floor of the fourth ventricle should raise suspicion for neuro‑Behçet disease【1】.

General Diagnostic Approach

• Patchy enhancement on brainstem MRI can be observed in both MS and RDD, underscoring the need for clinical correlation【5】.
• MRI alone cannot reliably differentiate among demyelinating, infectious, inflammatory, or neoplastic brainstem lesions; integration of clinical context, enhancement patterns, and serologic testing is essential【5】.

Complete spinal cord MRI (cervical and thoracic) is essential to detect asymptomatic cord lesions that strengthen an MS diagnosis【4】.
Lumbar puncture with oligoclonal band and IgG index analysis provides supportive evidence for MS【4】.