ETIOLOGY

Ataxia is an impairment of coordination or balance of voluntary movement. With few exceptions, this condition represents a disturbance of cerebellar pathways, including the cerebellar peduncles, spinocerebellar tract in the spinal cord, thalamic nuclei, and cortical reflections. The most common causes of acute ataxia in childhood are postinfectious acute cerebellar ataxia and drug intoxications. The differential diagnosis includes other disorders within the posterior fossa, such as tumors (medulloblastoma, ependymoma, cerebellar astrocytoma), multiple sclerosis, strokes, and hemorrhages. Other causes of recurrent or progressive ataxia, such as the paraneoplastic opsoclonus-myoclonus syndrome associated with neuroblastoma, inborn errors of metabolism, labyrinthine dysfunction, head trauma, epilepsy, postictal state, and migraine, can be difficult to diagnose and require special diagnostic testing for their identification. Congenital disorders also may produce chronic, nonprogressive ataxia (Table 183-1).

CLINICAL MANIFESTATIONS

The usual symptoms are a broad-based, unsteady gait (truncal ataxia) and intention tremor or dysmetria. An intention tremor worsens as the arm approaches the target. Overshooting or undershooting of the target is termed dysmetria (abnormality of distance). Classically, these symptoms stem from disorders of the cerebellar pathways, but peripheral nerve lesions causing loss of proprioceptive inputs to the cerebellum (Miller Fisher variant of Guillain-Barré syndrome) may present with similar symptoms.

Postinfectious acute cerebellar ataxia may follow chickenpox, infectious mononucleosis, or a mild respiratory or gastrointestinal viral illness by about 1 week. The pathogenesis is uncertain and may represent either a direct viral infection of the cerebellum or an autoimmune response directed to the cerebellar white matter and precipitated by the viral infection. Symptoms begin abruptly, causing staggering and frequent falling. Symptoms can progress to difficulty with standing and sitting. Truncal ataxia may be the only symptom or dysmetria of the arms, dysarthria, nystagmus, vomiting, irritability, and lethargy may be present. Symptoms usually peak within 2 days, then stabilize and resolve over 1 to 2 weeks. Cerebrospinal fluid (CSF) examination sometimes shows a mild lymphocytic pleocytosis or mild elevation of protein content. Brain imaging is usually normal. No specific therapy is available except to prevent injury during the ataxic phase. Recovery is usually complete.

DRUG INTOXICATION

Overdosage with any sedative-hypnotic agent can produce acute ataxia and lethargy, but ataxia without lethargy usually results from intoxication with alcohol, phenytoin, or carbamazepine. It is important to ask whether anyone in the household (family or visitor) is taking anticonvulsant or antipsychotic medications. Treatment is supportive.

POSTERIOR FOSSA TUMORS

Brain tumors are the second most common neoplasm in children. About 50% arise from within the posterior fossa. Tumors that arise in the posterior fossa or brainstem produce progressive ataxia with headache that may be acute or gradual in onset. There is a progressive worsening over days, weeks, or months. The ataxia and dysmetria may result from primary cerebellar invasion or from obstruction of the CSF pathways (aqueduct of Sylvius or fourth ventricle) with resultant hydrocephalus. The most common tumors in this region include medulloblastoma, ependymoma, cerebellar astrocytoma, and brainstem glioma.

PARANEOPLASTIC OPSOCLONUS-MYOCLONUS SYNDROME

Rarely a neuroblastoma located in the adrenal medulla or anywhere along the paraspinal sympathetic chain in the thorax or abdomen is associated with degeneration of Purkinje cells and the development of severe ataxia, dysmetria, irritability, myoclonus, and opsoclonus. An immunologic reaction directed toward the tumor may be misdirected to also attack Purkinje cells and other neuronal elements. The myoclonic movements are irregular, lightning-like movements of a limb or the head. Opsoclonus is a rapid, multidirectional, conjugate movement of the eyes, which suddenly dart in random directions. The presence of this sign should prompt a vigorous search for an occult neuroblastoma, including urine testing for adrenergic metabolites (vanillylmandelic acid and homovanillic acid), chest x-ray, abdominal ultrasound, and magnetic resonance imaging (MRI) with contrast enhancement of the entire sympathetic chain. These tumors tend to be localized and curable by surgical resection. Treatment of paraneoplastic opsoclonus-myoclonus can be difficult, but immunotherapy with corticosteroids or intravenous immune globulin (IVIG) often relieves the acute neurologic symptoms; 64% of children are left with persistent cerebellar deficits, and 36% have intellectual deficits.

INBORN ERRORS OF METABOLISM

Several rare inborn errors of metabolism can present with intermittent episodes of ataxia and somnolence. These include Hartnup disorder, branched chain ketoaciduria (maple syrup urine disease), multiple carboxylase deficiency (biotinidase deficiency), disorders of the urea cycle, and abnormalities of pyruvate metabolism.

LABYRINTHINE DYSFUNCTION

Difficulty walking with a severe staggering gait is one manifestation of labyrinthine dysfunction, but the diagnosis usually is clarified by the associated symptoms of a severe sense of spinning dizziness (vertigo), nausea and vomiting, and associated signs of pallor, sweating, and nystagmus.

MOVEMENT DISORDERS

Movement disorders or dyskinesias are a diverse group of entities associated with abnormal excessive, exaggerated, chaotic, or explosive movements of voluntary muscles. They are generally the result of abnormalities of the extrapyramidal system or the basal ganglia. Movement disorders in children are typically hyperkinetic patterns. The abnormal movements are activated by stress and fatigue and often disappear in sleep. They are typically diffuse and migratory (chorea), but may be isolated to specific muscle groups (segmental myoclonus, palatal myoclonus) and may not disappear in sleep.

Chorea is a hyperkinetic, rapid, unsustained, irregular, purposeless, nonpatterned movement. Muscle tone is decreased. Choreiform movement abnormalities may be congenital, familial, metabolic, vascular, toxic, infectious, or neoplastic in origin. The movements may occur alone or as part of a more extensive neurologic disorder (Sydenham chorea, Huntington chorea, cerebral palsy, Wilson disease, or reactions to toxins and drugs). Fidgety behavior, clumsiness, dysarthria, and an awkward gait may occur. The exact mechanism of dysfunction within the extrapyramidal system is unknown.

Athetosis is a hyperkinetic, slow, coarse, writhing movement that is more pronounced in distal muscles. Muscle tone may be increased. Athetosis is seen frequently in combination with chorea (choreoathetosis) and usually is present in conjunction with other neurologic signs. It may be seen in virtually all the disorders mentioned for chorea, but the most prominent cause is encephalopathy. Athetosis is a prominent feature of Hallervorden-Spatz disease, Wilson disease, and Pelizaeus-Merzbacher dystrophy. Many children with mixed forms of cerebral palsy have spasticity and choreoathetosis.

Dystonia is a hyperkinetic, sustained, slow, twisting motion (torsion spasm) that may progress to a fixed posture and can be activated by repetitive movement (action dystonia). It has many causes and associated neurologic signs. Dystonia usually begins in the legs when appendicular muscles are involved and in the neck or trunk when axial muscles are involved. Tardive dyskinesia usually is associated with antipsychotic drug use. Darting tongue movements, incessant flexion and extension of the distal muscles, standing and marching in place, and a perception of restlessness are common.

Tremor is a hyperkinetic, rhythmic, oscillatory movement caused by simultaneous contractions of antagonistic muscles. The amplitude and frequency are regular. In children, tremor is usually due to physiologic, familial, or cerebellar origin, but it may be seen in association with other disease processes (thyrotoxicosis, hypoglycemia, or Wilson disease) or drugs (bronchodilators, amphetamines, or tricyclic antidepressants).

Myoclonus is a hyperkinetic, brief flexion contraction of a muscle group, resulting in a sudden jerk. Myoclonus may be epileptic or nonepileptic. Nonepileptic myoclonus is distinguished from tremor in that it is a simple contraction of an agonist muscle, whereas tremor is a simultaneous contraction of agonist and antagonist muscles. Myoclonus is seen as a manifestation of various epilepsies and of infectious, toxic, and metabolic encephalopathies.

Tics are rapid, purposeless, involuntary, stereotyped movements and typically involve the face, eyes, shoulder, and arm. Most tic disorders in children are transient and not intrusive into the child’s life, but often are a source of great parental anxiety. Occasionally, tics are unmasked by stimulant agents. Persistent motor tics (>12 months) in association with vocal tics are characteristic of Tourette’s syndrome, a chronic tic disorder that usually begins before age 7 years. The prevalence is at least 5 in 10,000, with a male-to-female ratio of 4:1. The pathophysiology underlying tics is unknown, but a family history of tics is elicited in more than 50% of cases. The severity and pattern of the tics vary over months and years. Vocal tics begin later in the clinical course. The motor tics vary from muscle twitches (simple motor tic) and grunts (simple vocal tic) to complex stereotyped movement patterns (orchestrated movements). Co-morbid features, such as obsessive-compulsive disorder and attention-deficit/hyperactivity syndrome, may be present in half of children with Tourette’s disorder (see Chapters 13 and 19). Tic disorders are clinical diagnoses, and neurodiagnostic studies have limited value. Many children with tic disorders or Tourette’s syndrome are unperturbed by their tics and require no therapy. Others are quite disabled and may benefit from psychological support and pharmacologic therapy with α-adrenergic receptor agonists (clonidine) or neuroleptics (pimozide, haloperidol, risperidone). The natural history of Tourette’s disorder is favorable; about two thirds of children experience a significant reduction of tics or complete remission.