**Question:** Progressive multifocal leukoencephalopathy spares

A. Cerebellum
B. Motor cortex
C. Basal ganglia
D. Hippocampus

**Core Concept:** Progressive multifocal leukoencephalopathy (PML) is a rare demyelinating disease caused by the JC virus. The disease primarily affects the white matter of the brain, particularly the cerebral cortex and subcortical white matter.

**Why the Correct Answer is Right:** PML tends to spare the cerebellum, basal ganglia, and motor cortex due to the following reasons:

A. Cerebellum: The cerebellum is involved in motor coordination and balance, and its white matter is relatively less affected by the JC virus due to its low expression of the primary cellular receptor, polyoma virus T-antigen (PyVTA), which is required for viral entry.

B. Motor cortex: The motor cortex is responsible for voluntary motor function, and the white matter within this region is less commonly affected by PML due to its limited expression of PyVTA.

C. Basal ganglia: The basal ganglia are involved in motor control, planning, and coordination. In PML, the basal ganglia are less frequently affected due to their limited expression of PyVTA, which is essential for viral entry.

D. Hippocampus: The hippocampus is primarily involved in learning and memory, and its white matter is less frequently affected in PML because of its low expression of PyVTA.

**Why Each Wrong Option is Incorrect:**

Option A (cerebellum): Although the cerebellum is less affected, it is not completely spared, and some cases of PML have been reported involving the cerebellum.

Option B (motor cortex): While the motor cortex is less commonly affected, it has been reported to be involved in some cases of PML, making this option less accurate compared to A, C, and D.

Option C (basal ganglia): As mentioned above, the basal ganglia are less frequently affected due to their limited expression of PyVTA, but they have been reported to be involved in some cases of PML.

Option D (hippocampus): The hippocampus is less commonly affected, but it is not completely spared, and some cases of PML have been reported involving the hippocampus.

**Clinical Pearl:** The misconception of sparing the hippocampus in PML is a common pitfall among medical students. It is important to understand that while the hippocampus is generally less commonly affected, it is not entirely spared, and involvement has been reported in some cases of PML.