Extra-motor cerebral changes and manifestations in primary lateral sclerosis

Area of Science:

• Neuroscience
• Neurology
• Neurodegeneration

Background:

• Primary lateral sclerosis (PLS) is traditionally viewed as a pure upper motor neuron disease.
• Pathognomonic features include motor cortex atrophy and pyramidal tract degeneration.
• Extra-motor cerebral changes in PLS remain poorly understood.

Purpose of the Study:

• To systematically evaluate extra-motor cerebral changes in a cohort of Primary Lateral Sclerosis patients.
• To characterize the full spectrum of clinical and radiological manifestations in PLS.
• To reassess the definition of PLS based on observed neurobiological changes.

Main Methods:

• Prospective neuroimaging study of forty PLS patients.
• Standardized clinical, genetic, and imaging protocols were employed.
• Screening for ALS and HSP mutations, C9orf72 repeats, and comprehensive clinical/imaging assessments.

Main Results:

• PLS patients lacked known ALS/HSP-associated mutations and C9orf72 expansions.
• Voxel-wise analyses revealed significant grey and white matter alterations beyond the pyramidal system.
• Clinical assessment identified extra-motor manifestations including cognitive and behavioral deficits.

Conclusions:

• Primary lateral sclerosis is associated with widespread extra-motor changes.
• PLS should not be considered exclusively a disorder of the pyramidal system.
• Multidisciplinary management should account for these broader extra-motor manifestations.