Chapter 53: Ataxia

• Ataxia can result from a variety of lesions, including damage to the peripheral nerves, spinal cord, cerebellum, and cerebral hemispheres. One of the most common etiologies is drug intoxication, especially with alcohol, benzodiazepines, or phenytoin.

• Findings of cerebellar dysfunction include nystagmus, staggering, wide-based gait, and titubation. In addition, a sensory examination for light touch and pinprick, position, and vibration sense should be performed because lower-extremity sensory impairment can cause ataxia.

• In a patient with acute ataxia, the history and physical examination focus on excluding acute infectious etiologies, such as meningitis or encephalitis, lesions that result in increased intracranial pressure, such as hemorrhage and tumors, and toxic ingestions.

• A common cause of ataxia in children younger than 6 years is acute cerebellar ataxia, a postinfectious phenomenon that often occurs about 2 weeks after a viral illness. The onset of ataxia is insidious and predominantly affects the gait, although dysmetria, nystagmus, and dysarthria can occur.

• In children, the most common cause of intermittent ataxia is a migraine headache that involves the basilar artery. Besides ataxia, associated symptoms include blurred vision, visual field deficits, vertigo, and headache.

• Chronic/progressive ataxia has an insidious onset and progresses slowly over weeks to months. The differential diagnosis consists of brain tumors, hydrocephalus, and genetic disorders.

• The combination of ataxia, headache, irritability, and vomiting in a child younger than 6 years is characteristic of a brain tumor.

• Hereditary causes of ataxia include spinocerebellar ataxias, of which there are over 30 types. Friedrich's ataxia is common autosomal recessive ataxia, which usually manifests before 10 years of age. It is characterized by ataxia, nystagmus, dysarthria, kyphoscoliosis, cardiomyopathy, and absent deep tendon reflexes.

• Patients with progressive ataxia require a thorough evaluation in the emergency department (ED). All patients are examined for signs of increased intracranial pressure, which in some cases can be severe enough to result in the threat of uncal herniation.

Ataxia is a disorder of intentional movement, characterized by impaired balance and coordination. It is usually due to a cerebellar disorder, which variably affects the trunk or extremities. Severe truncal ataxia is sometimes referred to as titubation. Ataxia affecting the extremities can result in a wide-based gait or can cause dysmetria, which is the tendency of the limbs to overshoot a target, with subsequent movements attempting to correct the overshoot.^1–3

Ataxia is best classified as acute, episodic/intermittent, or chronic/progressive. Acute ataxia is usually acquired, whereas chronic/progressive usually is due to a congenital malformation, or a hereditary or degenerative disorder, although brain tumors can also result in progressive symptoms.^1–3

Ataxia can result from a variety of lesions, including damage to the peripheral nerves, spinal cord, cerebellum, and cerebral hemispheres. Lesions of the cerebellum can be further categorized as affecting the hemispheres, which results in ipsilateral limb hypotonia, tremor, and dysmetria, but spare speech. With walking, these patients tend to veer to the side of the lesion. Lesions of the midline vermis cause truncal ataxia or titubation, dysarthria, and gait abnormalities.^1–3 Damage to the spinal cord can cause ataxia when the patient stands with the eyes closed, which is referred to as a positive Romberg's sign (which tests proprioception). Patients with cerebellar ataxia have findings whether their eyes are open or closed.

Metabolic and systemic disorders can also cause ataxia. One of the most common etiologies is drug intoxication, especially with alcohol, benzodiazepines, or antiepileptic drugs.^2–5

True ataxia must be distinguished from problems with similar neurologic manifestations. Vestibular disorders can cause vertigo, a sensation of abnormal movement or spinning that can cause a severe gait disturbance, nausea, and vomiting. Vertigo is often accompanied by nystagmus. Myopathies can be confused with ataxia, as can peripheral neuropathies. On physical examination, myopathies are characterized by muscle weakness, whereas peripheral neuropathies are accompanied by decreased reflexes. Chorea is a disorder characterized by involuntary movements and incoordination. It is distinguished from ataxia in that it occurs at rest, whereas ataxia is manifested during intentional movement.

Physical Examination

Vital signs and a thorough physical examination should be performed. Any abnormalities such as bradycardia, hypertension, and an abnormal breathing pattern (Cushing's triad) should be recognized as being a sign of increased intracranial pressure, and treated immediately with bag-mask ventilation while preparing for rapid sequence intubation.

Findings of cerebellar dysfunction include nystagmus, staggering, wide-based gait, titubation, and speech abnormalities. Specific neurologic tests include the following:

• Finger to nose with eyes closed (to look for intention tremor)

• Finger to nose to (examiner's) finger; dysmetria is poor coordination of voluntary movements, and results in under- or overshooting the target (tests cerebellar integrity when limb strength and sensation is intact)

• Heel-to-shin maneuvers (test cerebellar integrity when limb strength and sensation are intact)

• Rapid alternating hand movements—difficulty is termed dysdiadochokinesia (tests cerebellar function)

• Heel and toe walking (with hemispheric lesions there is a tendency to veer in one direction)

• Tandem gait (with hemispheric lesions there is a tendency to veer in one direction)

• Walking in a circle (with hemispheric lesions there is a tendency to veer in one direction)^1,2

In addition, a sensory examination for light touch and pinprick, position, and vibration sense should be performed because lower-extremity sensory impairment can cause ataxia.

Other findings to check for include eye findings such as nystagmus, opsoclonus (neuroblastoma), or papilledema; neck findings including meningismus (CNS infection) or an ipsilateral head tilt (posterior fossa tumor); and ear findings including otitis media, and hearing loss (labyrinthitis).²

For diagnostic purposes, it is useful to categorize ataxia as acute, intermittent, or chronic/progressive (Table 53-1).

The particular studies should be based on the history and physical examination. A bedside glucose should also be done to rule out hypoglycemia. As ingestions are a major cause of acute ataxia, a urine toxicology screen for drugs of abuse, or serum levels for specific drugs (phenobarbital, phenytoin, carbamazepine, ethanol), or toxins (lead, carbon monoxide) may be warranted. Those patients with an altered level of consciousness, or focal neurologic findings, should have neuroimaging performed. An MRI scan is preferred, as not only does it show posterior fossa tumors better than a CT scan but it is also useful for strokes, demyelinating diseases, and some types of encephalitis. A CT scan is often more readily available and can be used to detect trauma, intracranial bleeding, tumors, and should be done prior to examination of the cerebrospinal fluid (CSF) if there is concern for increased intracranial pressure. CSF studies should be done when there is concern for infection, and may be useful for other causes of ataxia such as Guillain–Barré syndrome (GBS), and acute demyelinating encephalomyelitis (ADEM).^2,4,6

Acute ataxia generally has an onset of <24 hours. Drug toxicity and infections are the most common etiologies. Acute metabolic processes, such as hypoglycemia, are also implicated, although they are usually accompanied by multiple systemic manifestations.

In a patient with acute ataxia, the history and physical examination focus on excluding acute infectious etiologies, such as meningitis or encephalitis, recent infections, or immunizations; lesions that result in increased intracranial pressure, such as trauma, hemorrhage, and tumors; and toxic ingestions. Central nervous system infections are usually characterized by fever and headache, and often by mental status changes. The physical examination may reveal neck stiffness. Lesions that cause increased intracranial pressure are associated with headache and vomiting, and the physical examination may reveal papilledema.^2,4 In the case of a cerebellar hemorrhage, the onset of ataxia is extremely sudden, whereas with posterior fossa tumors, the history will usually reveal a more protracted process.² Cerebrovascular disease, such as a stroke, can also result in acute ataxia. This should be considered in those with hypercoagulable states and sickle cell disease.² Toxic ingestions are likely in patients on antiepileptic medications and are especially common in toddlers. Acute ataxia can also occur after head trauma, in which it can result from a cerebellar hemorrhage or basilar skull fracture.

Any ataxic patient in whom an acute infectious process (meningitis, encephalitis, cerebellar abscess) is considered requires a lumbar puncture. It is imperative that, prior to lumbar puncture, increased intracranial pressure be excluded by computed tomography (CT) scan of the brain.^1,2,4 In any case in which ingestion of a toxic substance is suspected, a toxicology screen is indicated. Urine screens are useful for drugs of abuse, whereas serum levels are needed for specific toxins that include antiepileptic medications, lead, carbon monoxide, and alcohol.

Certain causes of acute ataxia are almost unique to the pediatric population and deserve special mention. GBS can present with ataxia, although the associated findings of areflexia and, in the Miller–Fisher variant, ophthalmoplegia distinguish it from acute cerebellar ataxia. Many childhood illnesses and immunizations have been postulated as inciting an autoimmune phenomenon, which can result in acute cerebellar ataxia, ADEM, or brain stem encephalitis.¹

Acute Cerebellar Ataxia

A common cause of ataxia in children younger than 6 years is acute cerebellar ataxia. The onset of ataxia is insidious and predominantly affects the gait, although dysmetria, nystagmus, and dysarthria can occur. The affected child is afebrile, and has a normal level of consciousness. Acute cerebellar ataxia is thought to be a postinfectious phenomenon and often occurs 2 weeks after a viral illness. Ataxia has been reported after infection with varicella, influenza, mumps, Epstein–Barr virus, echovirus 6, coxsackie B virus, and other viruses. The gait abnormalities come on abruptly, and are maximum at onset, with the trunk affected more than the extremities.^1,6 It is a self-limiting illness with an excellent prognosis, usually resolving in the majority of cases in 2–3 weeks.⁶ Although therapies such as steroids and intravenous immune globulin have been used, there is really no specific therapy.⁶ Acute cerebellar ataxia is a diagnosis of exclusion.

Myoclonic Encephalopathy of Infancy (Opsoclonus/Myoclonus)

Myoclonic encephalopathy of infancy (polymyoclonus/opsoclonus) is another cause of acute ataxia. This syndrome occurs in children from 6 months to 3 years of age, in association with occult neuroblastoma.³ It is differentiated from acute cerebellar ataxia by its association with opsoclonus (rapid, chaotic conjugate eye movements), which occur in association with polymyoclonus (severe myoclonic jerks of the limbs and trunk or head).^1,3 Irritability and vomiting can also occur. Diagnostic tests that should be initiated in the emergency department (ED) include chest and abdominal CT or MRI, urine vanillylmandelic acid (VMA), and homovanillic acid (HVA).^1,3 Treatment for a neuroblastoma should be in consultation with a pediatric oncologist.^1,3

Acute Postinfectious Demyelinating Encephalomyelitis

This is a multifocal immune-mediated encephalopathy characterized by ataxia, alteration in level of consciousness, and neurological deficits. Seizures, cranial neuropathies, hemiparesis, sensory deficits, and transverse myelitis are common. These latter findings help distinguish ADEM from acute cerebellar ataxia.² The patient may have fever, headache, and meningismus. It develops during the recovery from a viral illness, or after vaccination. Repeated episodes of this should prompt a workup for multiple sclerosis.^1,2

Tumors

Up to 60% of childhood brain tumors occur in the brain stem or cerebellum. Those that arise in the posterior fossa often have a slow onset of symptoms including ataxia, headache, and vomiting. However, hydrocephalus from obstruction or a bleed into the tumor can cause abrupt symptoms and decompensation.^1,2 The most common tumors of the posterior fossa are cerebellar astrocytoma, brainstem glioma, ependymoma, primitive neuroectodermal tumor, and medulloblastoma.^3,7

Guillain–Barré Syndrome/Miller–Fisher Syndrome

This is an acute demyelinating polyradiculoneuropathy that occurs after an infection or immunization. Although it predominantly affects the motor nerves resulting in weakness, 15% of patients develop a loss of sensory input to the cerebellum resulting in a sensory ataxia. The ataxia and weakness is progressive over several days. The Miller–Fisher syndrome is a form of GBS that results in ataxia, areflexia, and ophthalmoplegia. It occurs 5 to 10 days after an infectious illness, especially Campylobacter gastroenteritis.^1,2 Diagnostic tests include lumbar puncture looking for cytoalbuminologic dissociation and anti-GQ1b antibody for the Miller–Fisher variant. Patients suspected of these syndromes should be admitted to the hospital for further testing and monitoring as disease progression is variable. Electromyography and nerve conduction studies are helpful to diagnose GBS where specific abnormalities are seen. It is less helpful in diagnosing the Miller–Fisher syndrome, but may demonstrate abnormalities.¹

Intermittent/Episodic Ataxia

Intermittent or episodic ataxia occurs as acute episodes that are similar in nature. In children, the most common cause of intermittent ataxia is a migraine headache that involves the basilar artery. Besides ataxia, associated symptoms include blurred vision, visual field deficits, vertigo, and headache. In a child experiencing the first basilar migraine, it is essential to exclude an acute infectious process, toxic ingestion, or mass lesion.¹

Partial complex seizures can also cause intermittent ataxia but are often associated with alteration of consciousness and possibly characteristic motor manifestations.

Rarely, inborn errors of metabolism result in intermittent ataxia. These include maple syrup urine disease, Hartnup disease, urea cycle defects (citrullinemia, ornithine transcarbamylase deficiency, and argininosuccinic aciduria), multiple carboxylase deficiencies (biotinidase deficiency and isovaleric acidemia), pyruvate decarboxylase and pyruvate dehydrogenase deficiencies.^1,8

Patients with intermittent ataxia may not require radiographic or laboratory evaluation in the ED if they present with a known diagnosis. Patients suspected of having seizures are referred for an electroencephalogram (EEG). The rare patient suspected of having an undiagnosed inborn error of metabolism is referred to a pediatric geneticist or endocrinologist.

Chronic/progressive ataxias have an insidious onset and progress slowly over weeks to months. The differential diagnosis consists of brain tumors, hydrocephalus, and hereditary disorders.

The combination of ataxia, headache, irritability, and vomiting in a child younger than 9 years is characteristic of a cerebellar tumor.^3,7 Cerebellar astrocytomas are located in the cerebellar hemispheres and cause ipsilateral limb ataxia, headache, and double vision. They occur most commonly in school-age children. Brain stem gliomas present with ataxia and are often accompanied by cranial nerve palsies or spasticity. Medulloblastomas present with headache, vomiting, and an unsteady gait.⁷ In some cases, posterior fossa tumors have a relatively acute presentation.

Hydrocephalus, whether congenital or acquired, can cause ataxia. It is often accompanied by headache and vomiting and, when the patient presents late in the course of illness, can be associated with critically increased intracranial pressure.

There are numerous types of hereditary ataxias, which includes inborn errors of metabolism (autosomal recessive inheritance), and degenerative ataxias (autosomal dominant and recessive, x-linked inheritance, as well as mitochondrial-related).⁸

Some of the inborn errors of metabolism cause intermittent ataxia, whereas others cause progressive ataxia. These storage diseases often present later in life, but many are now treatable. These include Refsum's disease and Bassen–Kornzweig syndrome (abetalipoproteinemia with hypovitaminosis A), which are treatable by diet (dietary restriction of phytanic acid and the addition of vitamin E, respectively).⁸ Wilson disease, which is due to copper accumulation, is treated with a chelation agent such as penicillamine D, whereas ataxia with vitamin E deficiency is treated with high doses of vitamin E.⁸ Leigh syndrome (subacute necrotizing encephalomyelopathy) consists of developmental delay or psychomotor regression with ataxia, dystonia, seizures, and lactic acidosis. It is thought to be due to a mitochondrial disorder.⁸

Other hereditary causes of ataxia include the autosomal dominant spinocerebellar ataxias, of which there are over 30 types.⁹ Each have cerebellar ataxia as a feature, and several have distinguishing features such as ophthalmoplegia, extrapyramidal signs, or seizures but the diagnosis is based on chromosomal analysis.⁹ Friedrich's ataxia is the most common autosomal recessive ataxia, which usually manifests before 10 years of age. It is characterized by slowly progressive ataxia, dysarthria, nystagmus, absent deep tendon reflexes, kyphoscoliosis, cardiomyopathy, weakness, diminished vibration and position sense, and abnormal glucose tolerance test.^3,10 Patients with ataxia–telangiectasia present with ataxia during the first year of life. They then develop abnormalities of eye movement (oculomotor apraxia), and telangiectasias of the blood vessels develop at 3–5 years of age, first occurring on the bulbar conjunctiva, then face, ears, and nose. Most children have an immunodeficiency and recurrent pulmonary infections. Diagnosis is by an elevated alpha-fetoprotein level.^3,10

Congenital cerebellar malformations of the brain can also cause ataxia, including aplasia or hypoplasia of the cerebellum, Dandy-Walker cysts, and Chiari malformations (Chiari type I malformation, herniation of the cerebellar tonsils into the foramen magnum; type II with downward displacement of the medulla with a lumbosacral meningomyelocele).^3,5

Patients with progressive ataxia require a thorough evaluation in the ED. All patients are examined for signs of increased intracranial pressure, which in some cases can be severe enough to result in the threat of uncal herniation. A CT scan or MRI of the brain is indicated in any patient with signs of a mass lesion or hydrocephalus. Many of these patients are candidates for an emergency placement of a ventricular shunt. Patients with suspected genetic diseases are referred to a pediatric geneticist for further evaluation and specific diagnosis (Fig. 53-1).²