Deciphering Spastic Ataxia: Clinical and Genetic Profiles.

Area of Science:

• Neurology
• Genetics
• Rare Diseases

Background:

• Hereditary cerebellar ataxia (HCA) and hereditary spastic paraplegia (HSP) exist on a clinical spectrum.
• Spastic ataxia, a combination of cerebellar syndrome and spasticity, is less understood with few identified genetic causes.
• This study investigates spastic ataxia within a large HCA cohort.

Purpose of the Study:

• To clinically and genetically characterize spastic ataxia in HCA patients.
• To compare spastic ataxia features with nonspastic HCA.
• To identify genetic underpinnings of spastic ataxia.

Main Methods:

• Prospective HCA cohort established in 2017 with standardized annual assessments.
• Spastic ataxia defined by ataxia and Modified Ashworth Scale spasticity grade ≥2.
• Clinical and genetic data analyzed and compared between spastic and nonspastic HCA groups.

Main Results:

• 56 out of 249 patients (22.5%) presented with spastic ataxia, showing earlier onset and longer duration.
• Spastic ataxia was linked to autosomal recessive inheritance and conventional variants, with 38 probands (80.8%) receiving a genetic diagnosis across 22 genes.
• Common diagnoses included ARSACS, ATX-SYNE1, ATX-ANO10, HSP/ATX-KIF1C, HSP/ATX-PGN, HSP-ZFYVE26, MxMD-ATP13A2, and ATX/HSP-KCNA2.
• Spastic ataxia patients exhibited more severe motor impairment (higher SARA scores) and frequent falls.

Conclusions:

• Spastic ataxia is a distinct HCA subgroup with recessive inheritance, genetic diversity, and severe motor deficits.
• Recognizing heterogeneous presentations and progressive nature is key for diagnosis, counseling, and management.
• Further research into spastic ataxia is warranted for improved patient outcomes.