Early Detection of Central Nervous System Involvement in ATTRv Using Multimodal MRI and Cognitive Assessments

Area of Science:

• Neurology
• Radiology
• Genetics

Background:

• Hereditary Transthyretin Amyloidosis with polyneuropathy (ATTRv-PN) is an inherited TTR gene mutation disorder.
• Amyloid deposition in ATTRv-PN affects peripheral nerves and shows significant central nervous system (CNS) involvement.
• Early detection of CNS damage in ATTRv-PN is crucial and necessitates advanced neuroimaging.

Purpose of the Study:

• To investigate cerebral white matter microstructural damage in symptomatic and presymptomatic ATTRv-PN patients.
• To evaluate the utility of multimodal MRI techniques in detecting CNS alterations in ATTRv-PN.
• To assess cognitive function differences between symptomatic and presymptomatic ATTRv-PN individuals.

Main Methods:

• Utilized comprehensive clinical assessments and multimodal MRI (FreeSurfer, TBSS, microbleed analysis).
• Included 30 symptomatic ATTRv-PN patients, 19 presymptomatic (pre-ATTRv-PN) patients, and 44 controls.
• Assessed cognition using the Addenbrooke's Cognitive Examination-Revised.

Main Results:

• ATTRv-PN patients exhibited diffuse subcortical white matter alterations.
• Cortical thinning and microbleeds were infrequent findings in the brain imaging.
• Symptomatic patients showed significantly lower scores in memory and verbal fluency compared to presymptomatic individuals.

Conclusions:

• ATTRv-PN is characterized by early-stage cerebral white matter microstructural damage.
• Multimodal MRI is an accurate, non-invasive tool for detecting CNS damage in ATTRv-PN.
• These findings enhance the understanding of the ATTRv-PN disease spectrum and CNS involvement.