Ataxia

Abstract

Balance and coordination are products of complex circuitry involving the basal ganglia, cerebellum and cerebral cortex, as well as peripheral motor and sensory pathways. Malfunction of any part of this intricate circuitry can lead to imbalance and incoordination, or ataxia, of gait, the limbs or eyes, or a combination thereof. Ataxia can be a symptom of a multisystemic disorder, or it can manifest as the major component of a disease process. Ongoing discoveries of genetic abnormalities suggest the role ofmitochondrial dysfunction, oxidative stress, abnormal mechanisms of DNA repair, possible protein misfolding, and abnormalities in cytoskeletal proteins. Few ataxias are fully treatable, and most are symptomatically managed. A discussion of the ataxias is presented here with brief mention of acquired ataxias, and a greater focus on inherited ataxias.

Ataxia in children: early recognition and clinical evaluation

“…The first syndrome is characterized by an enlargement of the fourth ventricle, the complete absence of cerebellar vermis and cystic formation near the internal base of the skull. In ACM, the affected children show a downwards displacement of the cerebellar tonsils through the foramen magnum with a presumed risk to complicate with a non-obstructive hydrocephalus.Multiple sclerosis in young children may initially manifest as intermittent ataxia [1, 3, 6]. …”

Neurogenomics in Africa: Perspectives, progress, possibilities and priorities

“…They are a group of inherited degenerative disorders of the central nervous system characterized by slowly progressive gait imbalance and incoordination resulting from dysfunctions of the cerebellum and its afferent and efferent connections. Many are polyglutamine or ‘CAG Triplet Repeat Disorders’ [57]. Usually classified by their mode of inheritance and causative gene or chromosomal locus, inheritance may be autosomal dominant [autosomal dominant cerebellar ataxias for which specific genetic information is known], autosomal recessive [Friedreich ataxia, ataxia-telangiectasia, ataxia with vitamin E deficiency, ataxia with oculomotor apraxia (AOA), spastic ataxia], or X-linked [SCAX1].…”

Characterisation of canine KCNIP4: A novel gene for cerebellar ataxia identified by whole-genome sequencing two affected Norwegian Buhund dogs

“…Hereditary ataxias are a group of movement disorders, typified by incoordination of gait, limbs, or eyes, primarily caused by inherited dysfunction of the cerebellum and/or its afferent or efferent pathways [1]. In humans autosomal recessive and dominant forms of hereditary ataxia have been reported, in addition to mitochondrial, and, in the case of fragile X tremorataxia, X-linked forms.…”

“…In humans autosomal recessive and dominant forms of hereditary ataxia have been reported, in addition to mitochondrial, and, in the case of fragile X tremorataxia, X-linked forms. Inherited ataxias are typically not curable and there are often not any disease-modifying treatments available [1,2].…”

“…Hereditary ataxias in humans are classified by mode of inheritance, whereas in dogs, where the underlying genetic basis is often less well defined, have recently been classified based on the clinical signs and the neuronal structures affected [1,3]. The five classes of canine hereditary ataxia are cerebellar cortical degeneration (CCD), spinocerebellar degeneration, canine multiple system degeneration (CMSD), cerebellar ataxias without significant neurodegeneration, and episodic ataxias [3].…”