Prodromal spinocerebellar ataxia type 2: Prospects for early interventions and ethical challenges

Mov Disord. 2017 May;32(5):708-718. doi: 10.1002/mds.26969. Epub 2017 Mar 3.


The characterization of prodromal stages in neurodegenerative disorders is becoming increasingly important because of the need for early neuroprotective therapies. Research during the past 3 decades in spinocerebellar ataxia type 2 has revealed a large body of evidence suggesting that many disease features precede the manifest cerebellar syndrome, which delineates the prodromal stage of this disorder. This stage is defined by clinical, imaging, and functional criteria, which are supported by early molecular events demonstrated in animal models. Knowledge regarding prodromal spinocerebellar ataxia type 2 provides insight into the mechanisms underlying neurodegeneration from the early stages, which enables the design of promising disease-modifying clinical trials through the identification of the optimum moment to begin the therapies, the appropriate selection of individuals, and the identification of sensitive outcome measures. The management of patients in prodromal spinocerebellar ataxia type 2 may raise ethical dilemmas related to predictive diagnosis and early interventions, which impose new challenges to clinical and therapeutic research. © 2017 International Parkinson and Movement Disorder Society.

Keywords: SCA2; early intervention; preclinical carriers; prodromal stage; spinocerebellar ataxia type 2.

Publication types

  • Review
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Ataxin-2 / genetics
  • Brain / diagnostic imaging
  • Early Diagnosis*
  • Early Medical Intervention / ethics
  • Early Medical Intervention / methods*
  • Ethics, Medical
  • Evoked Potentials, Auditory, Brain Stem
  • Evoked Potentials, Somatosensory
  • Eye Movement Measurements
  • Genetic Testing
  • Humans
  • Muscle Cramp / physiopathology
  • Neural Conduction
  • Olfaction Disorders / physiopathology
  • Polysomnography
  • Primary Dysautonomias / physiopathology
  • Prodromal Symptoms*
  • Reflex, Abnormal
  • Spinocerebellar Ataxias / diagnosis*
  • Spinocerebellar Ataxias / genetics
  • Spinocerebellar Ataxias / physiopathology
  • Spinocerebellar Ataxias / therapy
  • Transcranial Magnetic Stimulation


  • ATXN2 protein, human
  • Ataxin-2