Ataxia

Etiology

Ataxia may occur due to abnormalities in the nervous system's different areas, including the brain, spinal cord, nerves, and nerve roots. The different types of ataxia often have similar or overlapping causes in the same patient.[3]

• Focal lesions - due to tumors, stroke, multiple sclerosis, or inflammation
• Metabolic - due to substances such as alcohol, antidepressant drugs, and antiepileptic drugs
• Poisoning - due to radiation
• Vitamin B12 deficiency
• Thyroid disease - hypothyroidism
• Head injury
• Celiac disease (gluten ataxia)
• Hereditary - Friedreich ataxia, ataxia-telangiectasia, Niemann-Pick disease, fragile X associated ataxia/tremor syndrome 
• Arnold-Chiari malformation
• Wilson disease
• Succinic semialdehyde dehydrogenase deficiency

Epidemiology

The overall prevalence of ataxia is 26 cases per 100,000 in children. The overall prevalence rate of hereditary ataxias is 10 cases per 100,000 individuals.[4] Dominant cerebellar ataxia is present in 2.7 cases per 100,000 individuals, and recessive hereditary cerebellar ataxia in 3.3 per 100,000 individuals.[5] An increased prevalence occurs in countries where consanguinity is a common practice.[6] The worldwide prevalence of spinocerebellar ataxias is 3 to 5.6 cases per 100,000 individuals.[7] The most common spinocerebellar ataxia is spinocerebellar ataxia type 3.[8]

Pathophysiology

Ataxia may be due to an interference in the sensory transmission to the cerebellum caused by a lesion. This condition can lead to sensory or spinal ataxia. An interruption in cortical signals from the cerebellum causes cerebellar ataxia. Spinocerebellar ataxias are a result of both of the above mentioned pathologies. They are autosomal dominant and result from CAG repetition on chromosomes.

Friedreich's ataxia is the most common of the inherited ataxias. It has an autosomal recessive pattern of inheritance. It involves the frataxin gene. There is degeneration of peripheral nerve axons and loss of sensory cells. Patients present between the first and second decades of life. Multisystem abnormalities are present and include, gait ataxia, loss in proprioception, sensory loss, pes cavus, spastic extensor plantar responses, atrophy of extremities, and cardiomyopathy. Patients may also have diabetes mellitus, vision loss, and hearing loss.[9][10]

Depending on the location of the lesion, characteristic findings are as follows:

• Lesions in the lateral cerebellum cause symptoms on the same side as the lesion (ipsilateral), whereas diffuse lesions cause generalized symptoms.
• Lesions in the cerebellum hemisphere cause limb ataxia.
• Lesions in the vermis cause truncal, gait ataxia with sparing of the limbs.
• Lesions at vestibulo-cerebellar areas cause disbalance, vertigo and gait ataxia.[11]

History and Physical

Adequate history and examination are crucial parts in evaluating, assessing the location of the lesion, and treating patients with ataxia. The medical history should include age, gender, neurological, drug, toxin, and occupational exposures. Family history is essential. Systems review should assess the presence of constitutional symptoms such as fever, weight loss, and night sweats. A past medical history of diabetes, hypertension, and neurological diseases is essential.

Clinicians should ask the patients if any of the symptoms and signs are present, the level of functional disability in activities of daily living, onset, and progression. Common signs and symptoms include abnormalities in gait, slurred speech, difficulty in walking, abnormal eye movements, difficulty swallowing, increased fatigue, incoordination in fine motor movements such as handwriting, buttoning shirts, typing, tremors, vertigo, and problems in cognition.[11]

A general and neurological physical examination is an integral part of the evaluation. A complete neurological examination, including mental status, cranial nerves, and cerebellar examination, is critical. Grading and level of functional disability are assessable with the use of scoring systems such as the International Cooperative Ataxia Rating Scale, Brief Ataxia Rating Scale (BARS), and for patients with Friedrich's ataxia, the Friedreich's Ataxia Rating Scale.[12][13][14]

Evaluation

The necessary tests are guided by clinical presentation and clinical suspicion. Blood tests for specific deficiencies, drugs, and toxins may be in order. Urinalysis can look for mercury level measurement.

Brain imaging includes a computed tomographic scan as an initial study, but magnetic resonance imaging (MRI) is critical to visualize structural lesions, strokes, and congenital or acquired abnormalities. Imaging of the spinal cord with MRI is indicated if a spine lesion is suspected.

Genetic testing is the diagnostic course for inherited ataxias.

Treatment / Management

Currently, there is no curative treatment available for hereditary ataxia.  Depending on the causes, if the ataxia results from a stroke, toxic substances, hypothyroidism, or any modifiable risk factors, treatment is targeted at the specific condition causing ataxia. Some treatable causes are reversible by medication such as vitamin E, coenzyme Q10 deficiencies, and episodic ataxia type two.[15](B3)

Patients may use devices to reduce functional disability, such as walking aids, canes, wheelchairs, and walkers. Patients can receive physical, speech therapy, and symptomatic treatment. Medications can reduce tremors, muscle stiffness, and sleeping disorders. There is evidence that physical and mental exercises can improve the lives of patients with ataxia.

Differential Diagnosis

• Alcohol use
• Ischemic stroke
• Cerebellar hemorrhage
• Drug-induced
• Toxicity
• Hypoxia or heat stroke
• Von Hippel-Lindau syndrome

Prognosis

The prognosis largely depends on the type and cause of ataxia. Patients with progressive ataxia may suffer from worsening symptoms over the years and require symptomatic treatment. Hereditary ataxia has a shorter life expectancy; however, some people live up to the fifth or sixth decade. Severe forms may lead to death in childhood or the early years.

If the cause is acquired, for example, alcohol or drug-induced ataxia, the underlying cause needs to be treated, and triggering factors removed to improve prognosis.

Complications

Complications of ataxia are related to the type of ataxia. Commonly, patients have rigidity, dyspnea, breathing difficulty, and choking, which may also lead to death in severe cases. Patients may require assistance in ventilation, feeding tubes, and airway management. Patients who are unable to walk or require wheelchair assistance may develop pressure ulcers, infections, and thrombosis.

Psychological and psychiatric illnesses, such as dementia and depression, are common and require therapy. Other complications include lightheadedness, spasticity, tremors, lethargy, generalized pain, blood pressure changes, bowel, bladder, and sexual dysfunction.