A novel clinicopathologic entity causing rapidly progressive cerebellar ataxia?

Area of Science:

• Neurology
• Neuroscience
• Pathology

Background:

• Sporadic adult-onset cerebellar ataxia encompasses various conditions, often termed cortical cerebellar atrophy (CCA), idiopathic late-onset cerebellar ataxia (ILOCA), or sporadic adult-onset ataxia of unknown etiology (SAOA).
• These conditions are characterized by cerebellar cortex degeneration, slow progression, and absence of known causes like multiple system atrophy or inherited ataxias.

Purpose of the Study:

• To describe two patients with rapidly progressive sporadic adult-onset ataxia exhibiting extracerebellar symptoms suggestive of prion disease.
• To propose a new disease entity, rapidly progressive cerebellar cortical and thalamic degeneration, based on unique clinical and pathological findings.

Main Methods:

• Clinical case description and pathological reevaluation of two patients.
• Whole genome sequencing to identify potential genetic causes.

Main Results:

• Pathological findings were consistent with CCA but included additional thalamic degenerative changes.
• Whole genome sequencing did not reveal pathogenic variants associated with cerebellar ataxia in the studied patients.
• The disease course was rapidly progressive, unlike typical CCA.

Conclusions:

• Rapidly progressive cerebellar cortical and thalamic degeneration may represent a distinct disease entity.
• The underlying etiology remains unknown, necessitating further investigation and recognition.
• Highlighting clinical and pathological features aims to improve diagnosis and research for this rare ataxia.