Limb Ataxia

Limb ataxia can be caused by several factors including genetic mutations, referred to as hereditary ataxias (e.g., Friedreich ataxia, Ataxia-telangiectasia, spinocerebellar ataxias). Hereditary ataxias are classified by the causative gene and their pattern of inheritance, for example Friedreich ataxia is a neurodegenerative disorder caused by loss-of-function mutations in the frataxin (FXN) gene that is inherited in an autosomal recessive manner (i.e., child inherits one copy of a mutated gene from each parent). Ataxia-telangiectasia is another autosomal recessive disorder caused by mutations in the ataxia-telangiectasia mutated (ATM) gene resulting in defective deoxyribonucleic acid (DNA) repair. Lastly, spinocerebellar ataxias are autosomal dominant conditions (i.e., child inherits one copy of the mutated gene from one parent) caused by mutations in several possible genes often due to a repeat expansion mutation. For example, spinocerebellar ataxia type 1 (SCA1) is caused by a cytosine-adenine-guanine (CAG) repeat expansion in the coding region of the ataxin 1 (ATXN1) gene. 

Other medical conditions can cause limb ataxia including Huntington disease, a neurodegenerative disease caused by a mutation in the huntingtin gene, resulting in many CAG repeats. A group of disorders called acquired ataxias, refers to ataxias that do not have an underlying genetic basis and occur from an illness or autoimmune condition. An example includes multiple sclerosis, an autoimmune condition attacking the nervous system, resulting in demyelination (i.e., destruction of the protective covering surrounding nerve fibers). Another cause of acquired ataxia includes cerebellar stroke, or blockage of blood flow to the cerebellum, the posterior portion of the brain responsible for controlling balance and coordination. This usually occurs with disruption of blood flow through the posterior inferior cerebellar artery (PICA), specifically. Additionally, isolated lesions of the inferior cerebellar peduncle (ICP) in the medulla (i.e., lowest portion of the brainstem) may also cause this.  

In some cases, the cause of limb ataxia is unknown, such as in idiopathic late onset cerebellar ataxia (ILOCA). This is a non-genetic condition with an unknown cause that results in parts of the brain deteriorating gradually over time, starting around the age of 50. 

The signs and symptoms of limb ataxia include dysmetria (i.e., inability to judge the distance, range, direction, speed of a body part during active movement), dyssynergia (i.e., disruption of normal coordination), and intention tremor (i.e., rhythmic tremor worsened during purposeful motor movement). Limb ataxia may also result in functional impairment; for example, the individual may have difficulty with writing, picking up small objects, or buttoning clothes.  

When the cause is secondary to cerebellar strokes, the ipsilateral (i.e., same side) limb is affected (e.g., stroke on the left side of the cerebellum results in left arm ataxia). Oftentimes, people with ataxia may have to slow down their hand movement to reach objects accurately. Depending on the cause of limb ataxia, the onset may be slow, progressive, and chronic (e.g., hereditary ataxia) or it may be acute (e.g., cerebellar infarction).  

Limb ataxia can be diagnosed via physical examination by a healthcare professional. The clinician may ask questions to characterize the ataxia, such as the duration of symptoms (i.e., acute versus chronic), rate of progression (i.e., episodic ataxia versus progressive), aggravating factors (e.g., movement), and if there are any associated features (e.g., headache, vomiting, visual deficits, auditory involvement). The clinician often obtains a medical history to assess for cause (e.g., infection, medications/intoxications, environmental exposures), and a family history which may suggest a genetic disorder. Parts of the physical examination for limb ataxia includes the finger‐to‐nose test which tests coordination and cerebellar function. In this test, the clinician asks the individual to touch their finger to the clinician’s finger and then back to their nose.  

Other components of the complete neurological examination include testing cranial nerve function, reflexes, strength, and sensation. Genetic blood tests are available to test for hereditary forms of limb ataxia, and whole exome or genome sequencing can also detect genetic changes.  

Limb ataxia is treated with supportive measures including physical therapy and occupational therapy, which can help individuals maintain the maximum level of function. Additionally, strength and flexibility training can also be helpful. Hereditary ataxias are often progressive, and individuals often eventually need adaptive devices to assist in ambulation and daily activities, including wheelchairs, long-term.   

Omaveloxolone is an oral medication approved by the US Food and Drug Administration (FDA) in February 2023 for the treatment of Frederich's ataxia in those 16 years of age and older. It’s primarily thought to act as an antioxidant and help cells combat oxidative stress. Other novel therapies include gene therapy; however, more research is needed. If the limb ataxia is due to an underlying condition such as multiple sclerosis, treating the disorder is indicated, like with disease-modifying therapies (e.g., interferon beta medications or corticosteroids).