Longitudinal diffusion imaging across the C9orf72 clinical spectrum

Area of Science:

• Neuroimaging
• Neurology
• Genetics

Background:

• Discrepancies between diffusion tensor imaging (DTI) and clinical scales in amyotrophic lateral sclerosis (ALS) may stem from symptom heterogeneity, including cognitive-behavioral dysfunction.
• C9orf72 gene expansion carriers exhibit a spectrum of motor and cognitive-behavioral symptoms, ranging from ALS to frontotemporal dementia, making them a valuable model for studying this heterogeneity.

Purpose of the Study:

• To investigate the relationship between symptom heterogeneity and DTI changes in C9orf72 mutation carriers.
• To explore how DTI alterations correlate with both motor and cognitive-behavioral deficits in this population.

Main Methods:

• Twenty-eight C9orf72 mutation carriers with diverse symptoms underwent clinical evaluations and DTI imaging.
• Follow-up evaluations included motor, executive, and behavioral assessments, along with disease staging using the King's college staging system.

Main Results:

• C9orf72 carriers showed widespread white matter integrity reduction compared to controls.
• ALS Functional Rating Scale (ALSFRS-R) and King's stage correlated with corticospinal tract DTI measures, while cognitive/behavioral scores correlated with frontal white matter diffusion.
• Over six months, DTI changes progressed anteriorly and from deep to superficial white matter.

Conclusions:

• Cognitive-behavioral deficits impacting extramotor white matter tracts may explain DTI-clinical measure discrepancies in ALS.
• Both ALSFRS-R and King's stage correlate with corticospinal DTI measures.
• Group-level DTI changes are detectable over a six-month period.