Ataxia is the predominant manifestation of many acquired and inherited neurologic disorders affecting the cerebellum, its connections, and the afferent proprioceptive pathways. This article reviews the phenomenology and etiologies of cerebellar and afferent ataxias and provides indications for a rational approach to diagnosis and management.
The pathophysiology of ataxia is being progressively understood and linked to the functional organization of the cerebellum. The impact of cerebellar diseases on different neurologic functions has been better defined and shown not to be limited to loss of motor coordination. The role of autoimmunity is increasingly recognized as a cause of sporadic cases of ataxia. Large collaborative studies of long duration are providing crucial information on the clinical spectrum and natural history of both sporadic ataxias (such as the cerebellar form of multiple system atrophy) and inherited ataxias. New dominant and recessive ataxia genes have been identified. On the therapeutic front, progress mostly concerns the development of treatments for Friedreich ataxia.
Ataxia is the clinical manifestation of a wide range of disorders. In addition to accurate clinical assessment, MRI plays a major role in the diagnostic workup, allowing us to distinguish degenerative conditions from those due to other types of structural damage to the cerebellar or proprioceptive systems. Diagnostic algorithms based on clinical features, imaging, and neurophysiologic and biochemical parameters can be used to guide genetic testing for hereditary ataxias, the diagnosis of which is likely to be greatly improved by the introduction of new-generation DNA-sequencing approaches. Some rare forms of ataxia can be treated, so their diagnosis should not be missed. Proven symptomatic treatments for ataxia are still lacking, but intensive physical therapy appears to be helpful.
Address correspondence toDr Massimo Pandolfo, Department of Neurology, Hôpital Erasme, Route de Lennik 808, 1070 Brussels, Belgium, firstname.lastname@example.org.
Relationship Disclosure: Dr Pandolfo receives unrestricted support for conferences from Santhera Pharmaceuticals and royalty payments from Athena Diagnostics, Inc, for Methods to Diagnose Friedreich Ataxia. Dr Pandolfo serves on the drug safety monitoring board of and receives research support from Repligen Corporation. Dr Manto receives honoraria from Cambridge University Press and Springer Science+Business Media, and receives research grants from the Communauté Française, the European Commission, and the Fonds de la Recherche Scientifique Belgium. Dr Manto serves as editor-in-chief of The Cerebellum and as associate editor of the Journal of NeuroEngineering and Rehabilitation.
Unlabeled Use of Products/Investigational Use Disclosure: Dr Pandolfo discusses experimental therapeutics for the treatment of inherited ataxias and immunomodulatory treatments for immune-mediated ataxias. Dr Manto reports no disclosure.
Supplemental digital content: Videos accompanying this article are cited in the text as Supplemental Digital Content. Videos may be accessed by clicking on links provided in the HTML, PDF, and iPad versions of this article; the URLs are provided in the print version. Video legends begin on page 1338.