What are the distinguishing MRI findings of Alexander disease, Dandy‑Walker malformation, Miller‑Dieker syndrome, and aqueductal stenosis?

MRI Findings in Alexander Disease, Dandy-Walker Malformation, Miller-Dieker Syndrome, and Aqueductal Stenosis

These four conditions have distinct and recognizable MRI patterns that allow confident differentiation: Alexander disease shows frontal-predominant white matter changes with specific periventricular T1 hyperintensity; Dandy-Walker malformation demonstrates cerebellar vermis hypoplasia with an enlarged posterior fossa cyst; Miller-Dieker syndrome presents with complete agyria and thickened cortex; and aqueductal stenosis shows isolated ventricular enlargement without posterior fossa or cortical abnormalities. 1, 2, 3

Alexander Disease MRI Characteristics

Alexander disease has five cardinal MRI features that enable diagnosis without brain biopsy when four of five criteria are met 1:

• Extensive cerebral white matter changes with frontal predominance are the hallmark finding, distinguishing this from other leukodystrophies 1
• Periventricular rim with high signal on T1-weighted images and low signal on T2-weighted images is pathognomonic and reflects dense accumulation of Rosenthal fibers 1
• Abnormalities of basal ganglia and thalami appear as signal changes on T2-weighted sequences 1
• Brain stem abnormalities involve the medulla and pons with T2 hyperintensity 1
• Contrast enhancement occurs in particular gray and white matter structures, including periventricular regions and basal ganglia 1

The frontal predominance is critical for diagnosis—if white matter changes are diffuse or posterior-predominant, consider alternative diagnoses 1.

Dandy-Walker Malformation MRI Characteristics

Dandy-Walker malformation requires all of the following features for definitive diagnosis 4:

• Large median posterior fossa cyst widely communicating with the fourth ventricle is the defining feature 4
• Small, rotated, raised cerebellar vermis positioned superiorly and anteriorly 4
• Upwardly displaced tentorium and torcular herophili 2, 4
• Enlarged posterior fossa with expansion of the posterior cranial vault 2, 4
• Antero-laterally displaced but apparently normal cerebellar hemispheres 4
• Normal brain stem without compression or distortion 4

Sagittal T2-weighted sequences are essential for evaluating vermis anatomy—the vermis may show either partial agenesis with preserved lobulation (better prognosis) or severe dysplasia with absent lobulation (poor prognosis when associated with other brain malformations) 4.

Critical Differentiating Features from Mimics

• Persistent Blake's cyst: Shows retrocerebellar fluid collection with midline communication to fourth ventricle but has an intact, normally positioned vermis 2
• Mega cisterna magna: Demonstrates enlarged posterior fossa fluid collection but with completely normal vermis and fourth ventricle 2, 5
• Retrocerebellar arachnoid cyst: Compresses and displaces the cerebellar hemispheres and fourth ventricle anteriorly, unlike Dandy-Walker where hemispheres are displaced laterally 2

Miller-Dieker Syndrome MRI Characteristics

Miller-Dieker syndrome represents the most severe end of the lissencephaly spectrum 3:

• Complete agyria (absent gyration) with figure-of-eight brain shape is characteristic, resulting from complete lack of sulci and wide, vertically oriented Sylvian fissures 3
• Markedly thickened cerebral cortex measuring 10-20mm (normal is 2-4mm) 3
• Smooth cortical surface without any visible sulcation in most severe cases 3
• Shallow, vertically oriented Sylvian fissures creating the pathognomonic figure-of-eight appearance on axial images 3

The 17p13.3 deletion (encompassing LIS1, YWHAE and other genes) causes this syndrome and is detected in 9% of lissencephaly cases 3. The key distinguishing feature from other lissencephalies is the severity—Miller-Dieker shows complete or near-complete agyria, whereas other lissencephalies may show pachygyria (broad, simplified gyri) 3.

Cortical Thickness Assessment

The cortex in Miller-Dieker syndrome shows a characteristic four-layered appearance on high-resolution MRI rather than the normal six layers, though this requires specialized imaging sequences 3.

Aqueductal Stenosis MRI Characteristics

Aqueductal stenosis presents with a distinct pattern of isolated hydrocephalus:

• Enlarged lateral and third ventricles with normal or small fourth ventricle is the defining pattern, indicating obstruction at the cerebral aqueduct 2
• Normal posterior fossa size and configuration, distinguishing it from Dandy-Walker malformation 2
• Normal cerebellar vermis and hemispheres 2
• Normal cortical gyration and thickness, distinguishing it from Miller-Dieker syndrome 3
• No white matter signal abnormalities (unless secondary to transependymal CSF flow from severe hydrocephalus) 2

Sagittal T2-weighted images are essential to directly visualize the narrowed or obliterated cerebral aqueduct 2.

Algorithmic Approach to Differentiation

When evaluating these conditions, follow this systematic approach:

Step 1: Assess the posterior fossa 2, 4

• If enlarged with cystic fourth ventricle and vermis hypoplasia → Dandy-Walker malformation
• If normal size → proceed to Step 2

Step 2: Assess ventricular size and pattern 2

• If lateral and third ventricles enlarged with small fourth ventricle → aqueductal stenosis
• If normal or uniformly enlarged → proceed to Step 3

Step 3: Assess cortical gyration 3

• If agyria/severe pachygyria with thickened cortex → Miller-Dieker syndrome
• If normal gyration → proceed to Step 4

Step 4: Assess white matter signal 1

• If frontal-predominant white matter changes with periventricular T1 hyperintensity → Alexander disease
• If normal → none of these four conditions

Common Diagnostic Pitfalls

Do not diagnose Dandy-Walker malformation without sagittal imaging—axial images alone can miss vermis hypoplasia and lead to misdiagnosis of mega cisterna magna or Blake's cyst 4.

Do not overlook the periventricular T1 hyperintensity in Alexander disease—this finding is pathognomonic and distinguishes it from other leukodystrophies that show only T2 hyperintensity 1.

Do not diagnose Miller-Dieker syndrome based on mild pachygyria alone—the syndrome requires severe agyria or near-complete agyria; milder forms suggest other lissencephaly syndromes 3.

Do not attribute hydrocephalus to aqueductal stenosis if the fourth ventricle is also enlarged—this pattern suggests communicating hydrocephalus or Dandy-Walker malformation rather than aqueductal obstruction 2.