Peripheral nerve involvement in hereditary cerebellar and multisystem degenerative disorders

Area of Science:

• Neurology
• Genetics
• Pathology

Background:

• Hereditary ataxias (HA) are progressive neurodegenerative disorders.
• Classifications evolved from pathological hallmarks to clinico-genetic models.
• Molecular genetics has significantly expanded the known genotypes of HA.

Purpose of the Study:

• To review peripheral nerve involvement across various hereditary ataxia classifications.
• To highlight common patterns and exceptions in nerve pathology.
• To discuss specific genetic mutations and their impact on nerve function.

Main Methods:

• Review of classical pathological classifications (spinal, OPCA, CCA).
• Analysis of clinico-genetic classifications (EOCA, ADCA, ILOCA).
• Examination of peripheral nerve involvement in ARCA, ADCA, and ILOCA.

Main Results:

• Peripheral nerve involvement is common in most HA, typically presenting as sensory or sensorimotor neuronopathy.
• Autosomal recessive cerebellar ataxia (ARCA) and autosomal dominant cerebellar ataxia (ADCA) frequently show nerve involvement.
• Idiopathic late onset onset cerebellar ataxia (ILOCA) is an exception with less common nerve involvement.

Conclusions:

• Peripheral nerve involvement is a significant feature in hereditary ataxias, varying by subtype.
• Specific genetic mutations, like sacsin in AR spastic ataxia, can cause unique nerve dysfunction patterns.
• Understanding nerve involvement aids in diagnosing and managing diverse hereditary ataxia syndromes.