Ataxia

By Marcello Cherchi, MD PhD

For patients

The term “ataxia” refers to incoordination that can affect the limbs, trunk and eyes, which in turn can adversely affect a person’s balance and walking. There are many types of ataxias. If your doctor suspects an ataxia, then they may consider checking various tests of balance function, and in some cases they may recommend brain imaging (typically a brain MRI), blood tests or genetic tests. The management of an ataxia depends on the specific type; a few types of ataxias are treatable, while most are not.

For clinicians

Overview

Ataxia can be defined as the inability to generate a normal or expected voluntary movement trajectory (which deficit is not attributable to muscle weakness, chorea, dystonia, myoclonus or tremor), and depending on the specific ataxia, this incoordination may affect movements of the limbs, trunk, tongue or eyes. There are many causes of ataxia (ischemic, toxic, nutritional deficiency, superficial siderosis, genetic, neurodegenerative, episodic, infectious, immune-mediated), and while they can sometimes be distinguished by history and physical examination, often the diagnosis may require instrumented studies, imaging or genetic testing. It is important to recognize ataxias that may be reversible (e.g., acute alcohol intoxication, gluten ataxia, Lyme disease), or can be arrested/retarded (e.g., para-infectious, paraneoplastic, vitamin deficiency) or managed (e.g., acetazolamide-responsive episodic ataxias); for the remaining ataxias that are not directly treatable, physical and occupational therapy are reasonable.

Introduction

Ataxia can be defined as a pathological incoordination of motor activity characterized by an:

“Inability to generate a normal or expected voluntary movement trajectory that cannot be attributed to weakness or involuntary muscle activity (chorea, dystonia, myoclonus, tremor) about the affected joints. Ataxia can result from impairment of spatial pattern of muscle activity or from impairment of the timing of that activity or both” (Singer et al. 2010).

The motor dysfunction of ataxia can “affect fundamental activities such as gaze, speech, gait and balance” (Mariotti et al. 2005). Thus, the chief features of ataxias are:

• What would otherwise be a smooth trajectory of intended movement disintegrates due to some combination of:
  • Dysmetria (improper modulation of amplitude)
  • Dysrhythmia (improper timing)
  • Dyssynergia (improper coordination and sequencing of movements)
• Affected functions can include:
  • Appendicular movements (limbs)
  • Midline movements (trunk, tongue)
  • Ocular movements
• The incoordination is:
  • Not due to muscle weakness
  • Not due to another movement disorder (such as chorea, dystonia, myoclonus, tremor)

Ataxia is not in itself a disease; it is a motoric abnormality that can be manifested by many diagnoses.

A comprehensive classification of ataxias is beyond the scope of this section, but broadly, the dimensions along which ataxias vary include:

• Demographics: Some ataxias tend to manifest in particular age ranges.
• Genetics: Some ataxias appear to be sporadic (i.e., have not yet been shown to be genetic), while others are firmly established as genetically mediated.
• Chronology:
  • Cadence: Some ataxias start abruptly (e.g., cerebellar stroke), while others develop insidiously (e.g. spinocerebellar ataxias).
  • Chronicity: Some ataxias are chronic (e.g., Friedreich ataxia) while others are episodic (e.g., episodic ataxia types 1 – 6).
• Permanence:
  • Many ataxias do not yet have any treatment.
  • Some ataxias are reversible (e.g., acute alcohol intoxication, gluten ataxia), while some can be retarded or arrested (e.g., ataxia from deficiencies of vitamins B1, B6, B12, or E).

There is a broad range of etiologies of ataxias. The following list is incomplete:

• Ischemic, such as cerebellar stroke.
• Toxic (e.g., acute alcohol intoxication).
• Nutritional deficiency (e.g., B1, B6, B12, E).
• Superficial siderosis.
• Genetic (e.g., spinocerebellar ataxias, CANVAS, Friedreich ataxia).
• Neurodegenerative and sporadic (such as most forms of olivopontocerebellar atrophy).
• Episodic channelopathies (e.g., episodic ataxia types 1 – 6).
• Infectious (e.g., Lyme disease).
• Immune-mediated (e.g., gluten ataxia).
• Autoimmune (e.g., para-infectious or para-neoplastic).

Epidemiology

The epidemiology will vary by the type of ataxia.

Genetics

Some ataxias are genetically mediated, while others appear sporadic.

Pathophysiological mechanism of disease

Broadly, ataxias often result from cerebellar dysfunction, but can also occur when there is diminished somatosensory input (“sensory ataxia”).

Clinical presentation

The clinical presentation of an ataxia depends on the underlying etiology.

Physical examination

Patients suffering from ataxia are sometimes referred to otoneurology or neuro-ophthalmology because of the ocular motor manifestations.

Ocular motor examination

Some, but not all, ataxias involve ocular motor abnormalities. Even when ocular motor abnormalities are present, such findings are usually insufficient to secure the diagnosis.

Testing: auditory

Auditory testing is occasionally helpful in diagnosing an ataxia (such as in superficial siderosis).

Testing: vestibular

Ocular motor testing may be helpful in the diagnosis of some types of ataxias.

Testing of the vestibulo-ocular reflex may be helpful in identifying vestibular weakness, which can occur in a number of ataxias, such as CANVAS, Friedreich ataxia, and some of the spinocerebellar ataxias (Cherchi 2024).

Testing: other

Because many ataxias are phenotypically similar, genetic testing is taking on an increasingly important role in diagnosis.

Imaging

Many (though not all) cerebellar ataxias may manifest with cerebellar atrophy, which is usually most easily detected on brain MRI.

Histopathology

Histopathology will vary according to etiology.

Differential diagnosis

Many ataxias can resemble each other, and thus are on each other’s differential diagnosis.

Management

There are few ataxias that can be reversed (e.g., acute alcohol intoxication, gluten ataxia, Lyme disease) or retarded (e.g., para-infectious, para-neoplastic, deficiencies of vitamins B1, B6, B12, or E), so it is important to recognize these.

It is also important to recognize the episodic ataxias, as some of these (types 1, 2, 3 and 5) are responsive to acetazolamide.

For the remaining ataxias, management is symptomatic. Physical therapy may help to improve function. Occupational therapy may help reduce fall risk.

Prognosis

For the few ataxias that can be treated or arrested, prognosis is better.

The remaining ataxias are primarily neurodegenerative in nature, and thus the prognosis is poor.

References

Cherchi M (2024) Possible mechanisms connecting cerebellar ataxias and bilateral vestibular weakness: diagnostic and therapeutic implications. Journal of Neurology 272: 14. doi: 10.1007/s00415-024-12794-3

Mariotti C, Fancellu R, Di Donato S (2005) An overview of the patient with ataxia. J Neurol 252: 511-8. doi: 10.1007/s00415-005-0814-z

Singer HS, Mink JW, Gilbert DL, Jankovic J (2010) 13 – Ataxia. In: Singer HS, Mink JW, Gilbert DL, Jankovic J (eds) Movement Disorders in Childhood. W.B. Saunders, Philadelphia, pp 139-153