A 35 year old man develops hemiparesis, ataxia, homonymous hemianopia, and cognitive deterioration. An MRI of the brain demonstrates widespread areas of abnormal T2 signal in the white matter. An electroencephalogram is remarkable for diffuse slowing over both cerebral hemispheres. Brain biopsy reveals demyelination with abnormal giant oligodendrocytes, some of which contain eosinophilic inclusions. This patient’s condition is most closely related to which of the following diseases?

**Core Concept**
The patient's condition is characterized by widespread demyelination, abnormal oligodendrocytes, and eosinophilic inclusions, indicating a neurodegenerative disorder affecting the white matter of the brain.

**Why the Correct Answer is Right**
The patient's symptoms, including hemiparesis, ataxia, homonymous hemianopia, and cognitive deterioration, are consistent with a progressive and diffuse brain disorder. The presence of abnormal giant oligodendrocytes with eosinophilic inclusions on brain biopsy is a hallmark of Alexander disease, a rare and fatal neurodegenerative disorder. This condition is caused by mutations in the GLIAL FIBRILLARY ACIDIC PROTEIN (GFAP) gene, leading to accumulation of abnormally phosphorylated GFAP protein in oligodendrocytes and subsequent demyelination.

**Why Each Wrong Option is Incorrect**
**Option A:** Multiple Sclerosis is an autoimmune disease characterized by focal areas of demyelination, but it does not typically involve giant oligodendrocytes or eosinophilic inclusions.

**Option B:** Progressive Multifocal Leukoencephalopathy (PML) is a rare and fatal viral disease caused by the JC virus, which primarily affects immunocompromised individuals. While it does involve demyelination, it does not typically involve abnormal oligodendrocytes or eosinophilic inclusions.

**Option C:** Canavan disease is a rare and fatal neurodegenerative disorder caused by mutations in the ASPA gene, leading to accumulation of N-acetylaspartic acid in the brain. However, it does not typically involve giant oligodendrocytes or eosinophilic inclusions.

**Option D:** Krabbe disease is a rare and fatal neurodegenerative disorder caused by mutations in the GALC gene, leading to deficiency of galactocerebrosidase and accumulation of psychosine in the brain. While it does involve demyelination, it does not typically involve giant oligodendrocytes or eosinophilic inclusions.

**Clinical Pearl / High-Yield Fact**
Alexander disease is a rare and fatal neurodegenerative disorder that typically presents in early childhood, but it can also occur in adults, often with a more gradual course.

**Correct Answer:** D. Krabbe disease

✓ Correct Answer: A. AIDS