Ataxia

Nawaz K.A. Hack, M.D.
Joseph S. Kass, M.D., J.D.

Basic Information

Definition

Although ataxia typically is used to describe an unbalanced, incoordinated gait, the term is commonly used more expansively to refer to a general incoordination of movement that can affect movements of the limbs, the trunk, the oropharyngeal apparatus used for swallowing and speaking, and eye movements. The most common presentation is a complaint of imbalance when walking, leading to falls or walking into walls. People with gait ataxia have a broad-based gait and have difficulty with tandem walking.

Synonyms

Gait instability
Loss of balance
Functional impairment

ICD-10CM CODES
R27.0	Ataxia, unspecified
G11.0	Congenital nonprogressive ataxia
G11.1	Early-onset cerebellar ataxia
G11.2	Late-onset cerebellar ataxia
G11.3	Cerebellar ataxia with defective DNA repair
G11.8	Other hereditary ataxias
G11.9	Hereditary ataxia, unspecified
G32.81	Cerebellar ataxia in diseases classified elsewhere
G60.2	Neuropathy in association with hereditary ataxia
I69.093	Ataxia following nontraumatic subarachnoid hemorrhage
I69.193	Ataxia following nontraumatic intracerebral hemorrhage
I69.293	Ataxia following other nontraumatic intracranial hemorrhage
I69.393	Ataxia following cerebral infarction
I69.893	Ataxia following other cerebrovascular disease
I69.993	Ataxia following unspecified cerebrovascular disease

Epidemiology & Demographics

Incidence

Hereditary ataxia can affect 1 in 50,000 people in the United States.

Peak Incidence

Can affect all age groups. Hereditary ataxias peak in young adulthood.

Ataxia after age 65 is commonly secondary to stroke.

Prevalence

13.9 per 10,000.

Predominant Sex and Age

Ataxia can affect both sexes in equal proportions.

Genetics

The most common type of inherited ataxia in the United States is Friedreich ataxia (FA), which is autosomal recessive. The second most inherited ataxia is autosomal dominant spinocerebellar ataxia (SCA) type 3.

Risk Factors

•

A positive family history of ataxia
•

Excessive alcohol use
•

Hypothyroidism
•

Anticonvulsant use
•

A history of celiac disease
•

A history of cerebrovascular disease

Physical Findings & Clinical Presentation

•

Most individuals will complain of double vision or a sense of the environment moving and then a sense of unsteadiness and eventually frequent falls. Speech may become unintelligible, and they are frequently asked to repeat themselves. A history of difficulty cycling or performing physical activities may be present.
•

Physical exam findings include slurred speech, nystagmus, square wave jerks, dysconjugate gaze, and ocular bobbing. Dysmetria and past pointing may be noted in the finger to nose and heel to shin testing. Dysdiadochokinesia may be noted on exam.
•

Gait is notable for wide-based and difficulty turning and possible easy falling to one side. Frequent truncal swaying and veering is present. Tandem gait is abnormal.

Etiology

•

Ataxia can be caused by hereditary, structural, immune, neoplastic, infectious, and metabolic factors.
•

Hereditary factors include mitochondrial diseases such as MELAS (mitochondrial encephalopathy, lactic acidosis, stroke-like episodes), MIRAS (mitochondrial recessive ataxic syndrome), the many spinocerebellar ataxias, ataxia telangiectasia, and Friedreich ataxia.
•

Structural causes may be due to lesions of the cerebellum such as stroke, neoplastic masses, demyelinating lesions, Arnold-Chiari malformation, cerebellar brain abscesses, or disease of cerebellar leptomeninges such as meningitis, carcinomatosis, and lymphomatosis.
•

Metabolic causes include hypothyroidism and vitamin E, B₁, and B₁₂ deficiency, alcohol, and celiac disease.
•

Immune causes include multiple sclerosis, postinfectious cerebellitis, gluten ataxia due to celiac disease, Hashimoto encephalopathy, Miller Fisher variant of Guillain-Barré syndrome, and paraneoplastic syndromes, most commonly subacute cerebellar degeneration associated with anti-Yo antibodies due to breast, ovarian, or uterine malignancies, but other paraneoplastic syndromes, such as anti-Hu associated with small cell lung cancer, can also manifest with cerebellar ataxia.

Diagnosis

Differential Diagnosis

•

Vitamin deficiency: B₁ (thiamine), B₆ (pyridoxine), B₁₂ (cobalamin), copper
•

Vitamin excess: B₆ (pyridoxine)
•

Alcoholism
•

Anticonvulsant use, such as phenytoin
•

Inherited metabolic disorder, such as Alexander’s disease
•

Severe large-fiber neuropathy
•

Epilepsy
•

Celiac disease
•

Wilson’s disease
•

Cerebral anoxia
•

Cerebral tumors
•

Stroke
•

Cerebellitis
•

Miller-Fisher variant of Guillain-Barré syndrome
•

Paraneoplastic cerebellar degeneration
•

Anti-GAD65 cerebellar ataxia
•

Leptomeningeal diseases affecting the cerebellum
•

Conversion disorder

Workup

•

The workup for ataxia should be systematic and should always look for easily reversible disorders. An algorithm for a diagnostic approach to patients with progressive ataxia is described in Fig. E1.

FIG.E1

Laboratory evaluation of a patient with a bleeding disorder in whom the history and physical examination suggest a congenital coagulation disorder. INR, International normalized ratio; VWF, von Willebrand factor.

Modified from Stein JH [ed]: Internal medicine, ed 5, St Louis, 1998, Mosby.
•

Always start with a family history and investigate for any family members that were affected. This may guide genetic testing.
•

Acute-onset ataxia warrants consideration of an acute stroke with appropriate brain imaging.
•

Brain imaging, preferably magnetic resonance imaging (MRI), is highly recommended.
•

A lumbar puncture may be necessary if either infection or autoimmune-mediated process is suspected.
•

If a malignancy is present, then consider an appropriate paraneoplastic panel. However, the paraneoplastic syndrome may precede the appearance of a malignancy on imaging, and a paraneoplastic panel for cerebellar degeneration may be appropriate once other more common etiologies have been ruled out.

Laboratory Tests

•

Complete metabolic panel, including liver function tests
•

Complete blood count with differential and peripheral smear
•

Thyroid function tests
•

HIV and RPR
•

Vitamin B₁₂ and vitamin E
•

Anti-tissue transglutaminase
•

Serum copper and ceruloplasmin
•

In selected cases: genetic testing for spinocerebellar ataxias, paraneoplastic panel for cerebellar degeneration, anti-GAD65 antibodies, anti-TPO antibodies, and lumbar puncture for cytology if leptomeningeal carcinomatosis is suspected.
•
Notes about laboratory testing:
1. ○
  
  Thiamine levels are not reliable for detecting thiamine deficiency. Thiamine pyrophosphate or erythrocyte transketolase activation may be better, but neither the sensitivity nor specificity of these tests has been established.
2. ○
  
  Total cholesterol must be measured concomitantly with vitamin E levels to interpret result of vitamin assay.
3. ○
  
  Low normal vitamin B₁₂ levels of up to 400 pg/ml range can still result in neurological dysfunction. Measuring methylmalonic acid and homocysteine levels is more sensitive in patients with low normal vitamin B₁₂ levels, with a high level suggesting vitamin B₁₂ deficiency.
4. ○
  
  Electromyography and nerve conduction studies are warranted when the ataxia is thought to be due to peripheral nerve demyelination or part of a myeloneuropathy causing both peripheral neuropathy and dorsal column dysfunction, leading to proprioceptive loss from a sensory ataxia.

Imaging Studies

•

MRI of the brain with and without contrast is preferable.
•

Computed tomography (CT) scan of the head if MRI is not feasible.
•

Cardiac echocardiogram is recommended for the inherited ataxias.

Treatment

Treatment of ataxia is highly variable. The best way to treat ataxia is to investigate the cause and, if treatable, then treat the underlying condition. For example, if there is a vitamin deficiency, then vitamin replacement is recommended.

However, sometimes the cause is genetic or unknown, and treatment is directed at minimizing complications, such as neuropathy or cardiac disease, and rehabilitative therapy for the ataxia and motor complications.

Nonpharmacologic Therapy

•

Rehabilitative services such as physical, occupational, and speech therapy are a necessary part of the treatment of all ataxias, and evidence suggests it does improve functional status for individuals affected by ataxia.

Acute General Rx

•

Abrupt and sudden ataxia should always be worked up for stroke, which includes following an established acute stroke protocol.

Chronic Rx

•

Search for the underlying cause and focus on symptomatic management to prevent future disabilities. Rehabilitative services are integral to long-term care. Always evaluate cardiac and renal function and check for signs of developing neuropathy.

Complementary and Alternative Medicine

•

There are currently no widely accepted or evidence-based forms of complementary medicine for ataxia.

Disposition

•

Reversible causes of ataxia may see rapid improvement in symptoms. Genetic ataxias tend to be progressive.

Referral

•

Always refer to a neurologist

Pearls & Considerations

Comments

Look for reversible causes.

Prevention

A gluten-free diet would be preferable for people with celiac sprue disease.

Patient/Family Education

Educate families on the need to be supportive and make the home environment safe.

Ferri – Ataxia