Assessment of ataxia

Ataxia is a neurological syndrome characterised by clumsy and unco-ordinated movement of the limbs, trunk, and cranial muscles. It results from pathology in the cerebellum and its connections, or in the proprioceptive sensory pathways. The list of causes of ataxia is extensive. Typically, ataxia is classified on the basis of whether it is hereditary or acquired. Ataxia may also be classified by age of onset (childhood versus adulthood) or by whether it is associated with other clinical features (e.g., seizures, dystonia, vision loss). Degenerative ataxia is the term used to denote ataxia related to cerebellar atrophy of both genetic and unknown causation. Other terms that have been used for this type of ataxia in a broad sense include spinocerebellar degenerations and olivopontocerebellar atrophy, but these are becoming obsolete. National Ataxia Foundation

Clinical signs

Cerebellar ataxia produces a characteristic set of signs. [1] Manto M-U. Clinical signs of cerebellar disorders. In: Manto M-U, Pandolfo M, eds. The cerebellum and its disorders. Cambridge, UK: Cambridge University Press; 2002:97-120. Gait is unsteady with tendency to falls, hand co-ordination is impaired, and the patient may experience dysarthria or dysphagia. There may also be ocular symptoms related to abnormal control of eye movements. Neurological examination shows dysmetria of limbs (inaccuracy of targeted movements), as shown by abnormal finger-chase using patient fingers or toes. The patient may display a kinetic tremor of limbs and an uncontrolled oscillation of limbs during relatively slow but targeted movements. Early stance and gait problems include the inability to do a tandem stance or stand with feet together; stance becomes broad-based and displays increased sway of the body. Tandem gait becomes impaired and, later, regular gait can be frankly ataxic with a broad-based and lurching quality. Eye movements show gaze-evoked or other types of nystagmus, abnormal pursuit of visually presented objects (jerky appearance due to intrusion of saccades into pursuit), and inaccurate saccades when the person is asked to move the eyes quickly towards a target (hypometric or hypermetric saccades). There is also a scanning type of dysarthria.

Sensory ataxia is characterised by lower-limb and upper-limb inco-ordination associated with lack of proprioception. Clinical signs include impaired vibration sense, as well as impaired position and kinaesthetic sense. Deep tendon reflexes are often absent, but eye movements and speech are not affected. In some patients, sensory and cerebellar features can co-exist.

Patients with ataxia as a major feature often exhibit additional non-cerebellar neurological signs, either because the lesion causing the ataxia extends beyond the cerebellum into neighbouring structures or because the degenerative condition involves structures beyond the cerebellum.

Epidemiology

There are no precise data regarding the prevalence of ataxia of all causes. [2] Polo JM, Calleja J, Combarros O, et al. Hereditary ataxias and paraplegias in Cantabria, Spain. An epidemiological and clinical study. Brain. 1991;114:855-866. http://www.ncbi.nlm.nih.gov/pubmed/2043954?tool=bestpractice.com [3] Leone M, Bottachi E, D'Alessandro G, et al. Hereditary ataxias and paraplegias in Valle d'Aosta, Italy: a study of prevalence and disability. Acta Neurol Scand. 1995;91:183-187. http://www.ncbi.nlm.nih.gov/pubmed/7793232?tool=bestpractice.com Epidemiological studies that focus on hereditary types of ataxia have shown a prevalence of around 10 per 100,000 population, and idiopathic ataxia probably outnumbers hereditary cases. [4] Muzaimi MB, Thomas J, Palmer-Smith S, et al. Population based study of late onset cerebellar ataxia in south east Wales. J. Neurol Neurosurg Psychiatry. 2004;75:1129-1134. http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1739172/pdf/v075p01129.pdf http://www.ncbi.nlm.nih.gov/pubmed/15258214?tool=bestpractice.com Because there are many causes of degenerative and inherited ataxias, each individual type of ataxia is relatively rare. In the case of genetic forms of ataxia, there are clusters of high incidence of specific types due to founder effects and ethnic and geographical variations in the prevalence of many mutations. [5] Schols L, Bauer P, Schmidt T, et al. Autosomal dominant cerebellar ataxias: clinical features, genetics, and pathogenesis. Lancet Neurol. 2004;3:291-304. http://www.ncbi.nlm.nih.gov/pubmed/15099544?tool=bestpractice.com

Aetiology

Ataxia may be acquired or genetic. The list of acquired causes is extensive and includes vascular, demyelinating, neoplastic, autoimmune, toxic, degenerative, compressive, and infectious aetiologies. In many of these, ataxia may be a major clinical finding or be overshadowed by other signs. Many acquired lesions can be easily identified on imaging studies. However, imaging studies may reveal only cerebellar atrophy, a non-specific finding, necessitating further diagnostic work-up.

Genetic ataxias may be further classified by their mode of inheritance, such as autosomal dominant, autosomal recessive, or X-linked. In many of the commonly identified genetic ataxias, the clinical picture is dominated by cerebellar signs. However, many inherited metabolic errors, especially in childhood, can have ataxia as a major or minor feature. Online Mendelian Inheritance in Man (OMIM) In general, genetic forms of ataxia result in cerebellar atrophy and atrophy of related structures, which can be seen on imaging studies.

Pathogenesis

The inherited ataxias have recently been the focus of increasing understanding of molecular mechanisms. [5] Schols L, Bauer P, Schmidt T, et al. Autosomal dominant cerebellar ataxias: clinical features, genetics, and pathogenesis. Lancet Neurol. 2004;3:291-304. http://www.ncbi.nlm.nih.gov/pubmed/15099544?tool=bestpractice.com [6] Fogel BL, Perlman S. Clinical features and molecular genetics of autosomal recessive cerebellar ataxias. Lancet Neurol. 2007;6:245-257. http://www.ncbi.nlm.nih.gov/pubmed/17303531?tool=bestpractice.com [7] Soong BW, Paulson HL. Spinocerebellar ataxias: an update. Curr Opin Neurol. 2007;20:438-446. http://www.ncbi.nlm.nih.gov/pubmed/17620880?tool=bestpractice.com [8] Jen JC. Hereditary episodic ataxias. Ann NY Acad Sci. 2008;1142:250-253. http://www.ncbi.nlm.nih.gov/pubmed/18990130?tool=bestpractice.com More than 40 distinct gene defects cause ataxia as a major feature, and recessive, dominant, X-linked, and mitochondrial mutations have been identified. A wide range of primary pathogenic mechanisms have been proposed, including oxidative stress, problems with respiratory chain function, cytoskeletal abnormalities, DNA repair abnormalities, chaperone protein dysfunction, protein misfolding and aggregation, and channel dysfunction, among others.

Disorders resembling ataxia

Many types of gait problem can superficially resemble ataxia. Examples include gait abnormalities from bilateral frontal lobe lesions (i.e., frontal ataxia or Brun ataxia) and occasionally dystonic gait. Gait disorders from muscle disease, neuropathies, and spinal cord problems can usually be easily differentiated by clinical examination.

Gait difficulties from lesions of the vestibular apparatus also need to be differentiated from cerebellar ataxia. The co-ordination problem in the limbs is in the nature of "past pointing" rather than true dysmetria, and eye movement problems are often confined to nystagmus in the primary position. Dysarthria is not a feature of vestibular disease, but nausea and oscillopsia can be a feature of vestibular lesions.

The presence of speech and oculomotor signs related to cerebellar pathology can clearly differentiate cerebellar ataxia from other types of inco-ordination.