Introduction to ataxia

Ataxia is a group of neurological disorders characterised by involuntary movements leading to gait abnormalities, balance issues, and difficulty with fine motor movements. Ataxia is mostly caused by damage to the cerebellum, and to any pathways that provide input or output to the cerebellum.¹ Damage can occur as a result of injury or illness, known as acquired ataxia, or because of degeneration of the cerebellum or spinal cord due to the inheritance of a mutated (changed) gene called hereditary ataxia. Acquired ataxia can be caused by: 

• Severe head injury 
• Bacterial brain infection 
• Viral infection 
• Conditions that disrupt blood to the brain (stroke, haemorrhage or a transient ischaemic attack (TIA))
• Cerebral palsy 
• Multiple sclerosis 
• Long-term alcohol misuse
• An underactive thyroid gland
• Deficiency in vitamin E or B12 
• Brain tumours and some types of cancer
• Toxic chemicals
• Medications like benzodiazepines - these occasionally trigger ataxia as a side effect

In terms of hereditary ataxia, there are various types divided according to their mode of inheritance and development of symptoms:

• Friedreich's ataxia - This is the most common type of hereditary ataxia, where symptoms usually begin to develop before age 25, and individuals slowly deteriorate from there
• Ataxia-telangiectasia - This is a rare form of hereditary childhood ataxia in which symptoms cause a quick deterioration
• Spinocerebellar ataxia - A group of hereditary ataxia that often doesn’t develop until adulthood
• Episodic ataxia - This is a rare type in which symptoms come and go; episodes usually last several minutes to hours

Sometimes, the cause of degeneration is unknown which is known as idiopathic late-onset cerebellar ataxia. This usually develops at around 50 years old and causes deterioration over time. 

Each form of ataxia has unique and specific symptoms, although there are common symptoms amongst groups of ataxia. The most commonly found symptoms of ataxia are:

• Poor coordination
• Poor balance
• Walking unsteadily and/or with feet very wide apart
• Difficulty with fine motor tasks 
• Dysarthria (increasingly slurred, slow or unclear speech)
• Back-and-forth eye movements that are uncontrollable
• Dysphagia (difficulty swallowing)

Neurological examination

To diagnose ataxia, your physician will first begin with a detailed medical history and physical examination. This is to determine if the ataxia is hereditary and understand the onset and progression of the disease to distinguish between the forms of ataxia. 

Physical examination

The physical examination assesses gait and posture. Coordination tests, such as the finger-to-nose test and heel-to-shin test, evaluate the control and normality of movements. Reflexes and muscle tone are assessed to eliminate other neurological disorders, for example, hypotonia or hypertonia, which may indicate specific pathologies. A sensory examination is used to check deficits in proprioception (pressure changes), which is often impaired in ataxic patients. In addition, cognitive function and speech performance are evaluated. The healthcare provider will check there are no deficits in memory or executive functions, as well as the normal patterns and control of speech.²

Lumbar puncture

An important neurological examination is the lumbar puncture, also known as a spinal tap. It involves a needle being inserted into your lower back between the 3rd and 4th or 4th and 5th lumbar vertebrae in order to obtain a sample of cerebrospinal fluid. The patient lies on their side, and a local anaesthetic is given to numb the area. In children a sedative is given to help them stay still. After the procedure, it is required to remain lying down for an hour, followed by rest and lots of fluid. A doctor will also examine the site of injection and ensure you can move your legs before you leave the hospital.³ 

The colour and components of the cerebrospinal fluid will then be examined. A healthy individual would have clear fluid, whereas bloody or cloudy fluid indicates bleeding or inflammation in the brain. The makeup of cerebrospinal fluid is then checked, including levels of proteins, glucose, lactate, etc. It is also tested for the presence of bacteria or other microorganisms which could cause disease.³ An abnormal cerebrospinal fluid sample will sometimes have pleocytosis (presence of lymphocytes) and occasionally elevated protein levels.⁴ Lumbar puncture findings are especially useful in cases where imaging and genetic tests do not provide definitive answers.

EMG 

An EMG (electromyogram) is a recording of the electrical activity of the nerves in muscle fibres at rest and during activity. During an EMG, needle electrodes are placed on the muscle, and electrical activity is recorded during periods of rest and movement. An EMG is used to distinguish a muscle disorder and a nerve disorder. They also help to determine key locations of nerve damage that can be associated with specific ataxias. An EMG is important for ataxia as in typical cases of Friedreich’s ataxia, over 92% of digital and 96% sural nerves have the absence of electrical activity.⁵  

Imaging

Imaging tests can be used to check for physical abnormalities in the brain that may be caused by types of hereditary ataxia. The most commonly used imaging tests for ataxia are:

• Computerised topography (CT)
• Magnetic resonance imaging (MRI)

CT

A CT scanner uses X-rays to generate comprehensive images of the body. A computer then compiles the images to create cross-sectional images of the bones, blood vessels and soft tissues. It can create images of a higher resolution than an X-ray. A CT scan is used to diagnose ataxia after a head injury or when blood vessel damage is suspected. It is also used if a patient presents with vertigo, where a CT scan of the inner ear is therefore appropriate. Whereas an MRI is used to best visualise the spinal cord and brain abnormalities. An MRI is used over a CT when there is no history of injury or stroke. 

MRI

An MRI uses powerful magnetic fields and radio waves to produce 3D images of the anatomy. They are suited for soft tissue and non-bony areas of the body. An MRI differs from a CT because they do not have ionising radiation of x-rays, making it less dangerous. In addition, an MRI provides a more detailed image of a higher resolution, particularly of the brain, spinal cord and connecting nerves, than a CT or X-ray would. In the brain, an MRI can discriminate between white matter and grey matter, which allows it to evaluate the extent of atrophy (degeneration) of brain regions. The major disadvantage is the expensive price of a test.

Various types of ataxia affect the brain differently, thus appearing on an MRI. Many hereditary ataxias involve the thinning of the spinal cord as well as the degeneration of the cerebellum. In particular, Friedreich’s ataxia and autosomal recessive spastic ataxia of Charlevoix-Saguenay are characterised by loss of spinal cord volume, but volume loss is not limited to these types.⁶ In addition to the spinal cord, the following areas of the brain are of key interest when identifying ataxia in an MRI:⁶

• Volumes of cerebellar compartments and sometimes the cortical thickness and cross-sectional area
• Brainstem
• Basal ganglia

Furthermore, measures of these areas are sensitive to adjustments in symptomatic patients to presymptomatic patients.⁵

Genetic testing

Genetic testing involves taking a blood sample and checking the DNA for mutations known to cause ataxia. There are known gene mutations for Friedreich's ataxia, ataxia-telangiectasia and two-thirds of spinocerebellar ataxia cases.7 Being able to identify the type of ataxia via genetic testing helps guide treatment and can provide information for family planning. Genetic testing is also used in pre-symptomatic people where there is a family history of the condition.

Types of genetic tests

Genetic testing has a variety of approaches:⁸

• Single gene testing - This involves testing for specific known mutations. It is useful when a particular type of ataxia is strongly suspected based upon clinical and family history
• Panel testing - Involves analysing multiple genes simultaneously. This approach is beneficial where the clinical presentation is unclear, thus, it could be due to mutations in several genes
• Whole exome sequencing (WES) - Analyses the coding regions (exome) of all genes. It is most advantageous to identify mutations in rare genes. However, it is prone to missing specific types of mutations
• Whole genome sequencing (WGS) - Provides a comprehensive analysis of the genome (all DNA). It is the most thorough method but is also more expensive and complex to interpret

Genetic counselling

If genetic testing is positive for the gene mutation attributed to ataxia, this can have many implications for a person's life. For this reason, patients will meet with genetic counsellors to discuss their results, potential consequences and options moving forward. Since the condition is inherited it often can influence a couple's decision to have children. Genetic counselling can tell how likely it is that a child will inherit the condition and alternative options if the patient wishes not to have biological children. Furthermore, if a pre-symptomatic individual undergoes genetic testing, it can have a great physiological impact knowing they will likely inherit a neurodegenerative disease. Support can be offered from genetics as well as a referral for counselling. 

Summary

Ataxia is a group of neurological disorders characterised by involuntary movements, leading to gait abnormalities, balance issues, and difficulty with fine motor tasks. It can be caused by damage to the cerebellum due to injury, illness (acquired ataxia), genetic mutations (hereditary ataxia), or an unknown cause (idiopathic ataxia). Diagnosis is tailored depending on the symptoms and clinical history of the patient. Diagnosis will always start with a physical exam, and if indicated further, neurological tests like lumbar puncture and EMG. Imaging tests like CT and MRI are also used to detect brain and spinal cord abnormalities. Genetic testing identifies if ataxia is hereditary and often diagnoses the specific type. Given ataxia's profound impact, patients might benefit from consultations with geneticists or therapists for comprehensive support and management.