A 62-year-old man presents with a 2-year history of progressive cerebellar ataxia, REM sleep behavior disorder, and severe orthostatic hypotension (40 mm Hg drop on standing without compensatory tachycardia). Examination reveals wide-based gait, scanning dysarthria, and limb dysmetria, with parkinsonism that responds poorly to levodopa. T2-weighted axial MRI through the pons shows the cruciform hyperintensity marked as **A** in the diagram. Which of the following best describes the pathological substrate underlying this MRI finding in this patient?

Explanation

## Why option 1 is correct The cruciform (cross-shaped) T2 hyperintensity marked **A** — the "Hot Cross Bun sign" — is pathognomonic for Multiple System Atrophy, Cerebellar type (MSA-C). This sign reflects degeneration of pontocerebellar fibers (transverse pontine fibers) while the corticospinal tracts and tegmentum are spared, creating the characteristic cross pattern. MSA is a sporadic adult-onset α-synucleinopathy distinguished from Parkinson disease by the presence of glial cytoplasmic inclusions (Papp-Lantos bodies) of α-synuclein in oligodendrocytes rather than neuronal Lewy bodies. The clinical presentation—cerebellar ataxia, autonomic failure (orthostatic hypotension without compensatory tachycardia, erectile dysfunction), poor levodopa response, and REM sleep behavior disorder—confirms MSA-C. The Hot Cross Bun sign is highly specific for MSA-C among the common neurodegenerative disorders (Bradley Neurology 8e; Movement Disorders Society MSA Diagnostic Criteria 2022). ## Why each distractor is wrong - **Option 2 (Neuronal Lewy bodies in Parkinson disease)**: While both MSA and Parkinson disease are α-synucleinopathies, Parkinson disease features neuronal (not glial) Lewy bodies and typically shows a good response to levodopa. This patient's poor levodopa response and early autonomic failure are red flags for MSA, not idiopathic PD. The Hot Cross Bun sign is not characteristic of PD. - **Option 3 (Central pontine myelinolysis)**: CPM occurs acutely due to osmotic stress (rapid correction of hyponatremia) and presents with acute neurological deterioration, locked-in syndrome, or death. This patient has a 2-year insidious progressive course with autonomic features and cerebellar signs incompatible with CPM. CPM does not produce the Hot Cross Bun sign. - **Option 4 (Pontine glioblastoma)**: A pontine glioma would present with acute/subacute focal deficits, mass effect, and hydrocephalus. The 2-year progressive course with systemic autonomic dysfunction, the specific pattern of the Hot Cross Bun sign (degeneration, not infiltration), and the poor levodopa response all exclude primary neoplasm. Glioblastoma does not produce this characteristic MRI pattern. **High-Yield:** The Hot Cross Bun sign = cruciform pontine T2 hyperintensity from selective degeneration of transverse pontine fibers in MSA-C; pathognomonic finding reflecting glial α-synuclein pathology (Papp-Lantos bodies in oligodendrocytes), not neuronal Lewy bodies. [cite: Movement Disorders Society MSA Diagnostic Criteria 2022; Bradley Neurology 8e]