Late-onset multiple system atrophy: Neuropathological features associated with slow disease progression.

Area of Science:

• Neurology
• Pathology
• Geriatrics

Background:

• Late-onset multiple system atrophy (LO-MSA), with symptom onset at age 75+, is more prevalent than previously thought.
• Clinicopathological characteristics of LO-MSA are not well-defined, necessitating further investigation.

Purpose of the Study:

• To elucidate the clinicopathological features of late-onset multiple system atrophy (LO-MSA).
• To compare the clinical and pathological differences between LO-MSA and usual-age-onset MSA (UO-MSA).

Main Methods:

• Compared clinical and histopathological features of 5 LO-MSA patients with 24 UO-MSA patients (similar disease duration).
• Assessed degeneration severity in striatonigral (StrN) and olivopontocerebellar (OPC) systems.
• Quantified neuron numbers in brainstem autonomic nuclei and spinal intermediolateral nuclei.
• Measured α-synuclein inclusion density in the putamen, inferior olivary nucleus, and ventrolateral medulla (VLM).

Main Results:

• Both LO-MSA and UO-MSA predominantly showed the MSA-olivopontocerebellar atrophy (OPCA) subtype.
• LO-MSA exhibited less severe StrN and OPC system degeneration compared to UO-MSA.
• LO-MSA had better preservation of brainstem autonomic neurons, particularly serotonergic neurons in the VLM (p=0.013).
• LO-MSA showed significantly lower α-synuclein inclusion density in the putamen (p<0.001).

Conclusions:

• Neuronal degeneration in LO-MSA appears to progress more slowly than in UO-MSA.
• The prognosis for LO-MSA may not be inherently worse than for MSA overall, especially with adequate medical management.