Brain diffusion tensor imaging changes in cerebrotendinous xanthomatosis reversed with treatment

Area of Science:

• Neuroimaging
• Genetics
• Metabolic Disorders

Background:

• Cerebrotendinous xanthomatosis (CTX) is a rare autosomal recessive disorder caused by CYP27A1 mutations, leading to lipid accumulation.
• Clinical manifestations include spastic paraparesis, epilepsy, cognitive decline, diarrhea, and cataracts.

Observation:

• Two siblings with CTX and CYP27A1 mutations were treated with chenodeoxycholic acid (CDCA).
• Clinical assessments, neuropsychological tests, laboratory tests, EEG, MRI, and DTI were used for evaluation before and after treatment.
• Conventional MRI showed no abnormalities, but DTI revealed reduced fractional anisotropy (FA) and tract density in the cerebellum and cerebrum.

Findings:

• CDCA therapy resolved chronic diarrhea, normalized cholestanol levels and EEG, and improved gait, cognition, and seizure control.
• Post-treatment DTI showed progressive increases in cerebellar tract density and cerebral FA.
• DTI detected neuroimaging changes indicative of treatment response, even when conventional MRI remained unchanged.

Implications:

• CDCA therapy can lead to significant clinical improvement and normalization of biomarkers in CTX patients.
• Diffusion tensor imaging (DTI) and tractography are sensitive tools for detecting early treatment-induced neuroplasticity in CTX.
• DTI may serve as a valuable neuroimaging biomarker for monitoring therapeutic efficacy in CTX, complementing conventional MRI.