Definition and Pathophysiology

Dystonia is an involuntary movement disorder characterized by sustained or intermittent muscle contractions that cause twisting and repetitive movements, abnormal postures, or both.¹ Muscle agonists and antagonists are affected simultaneously, as documented by electromyography. Dystonia may occur with voluntary movement or at rest. Voluntary movement of one body part may result in dystonia not only in that part but also in overflow to other regions. Children with dystonia typically have widely varying muscle tone; at times they are described as being “loose as noodles” and at other times as “stiff as a board.” Dystonia is often misdiagnosed as spasticity or athetosis; the distinction is important because treatment and outcomes of the two movement disorders are so different.

Dystonia is attributed to abnormalities in the cortical–basal ganglia–cortical circuits and, particularly in children, is often secondary to structural lesions, especially lesions in the putamen. Such lesions result in decreased firing and more erratic firing of neurons in the internal globus pallidus (GPi) such that synchronization of reentrant circuits is altered and the supplementary motor cortex and premotor cortex are excessively stimulated.² Output of the GPi is often minimal at rest but excessive with movement. Sensory fields are enlarged and scaling of movement is altered. Although dystonia in adults occasionally results from lesions in sites other than the basal ganglia, including the brainstem, spinal cord, and peripheral nerves, involvement of sites other than the basal ganglia is rare in children.

Classification, Grading, and Causes

Dystonia was initially described in 1911 by Oppenheim, who labeled the disorder dystonia musculorum deformans.³ The term was subsequently altered to idiopathic torsion dystonia. Pediatric dystonia may be classified by etiology or by site or sites of involvement.^1,4 Primary dystonia develops without any evident cause. In children with primary dystonia, magnetic resonance imaging of the brain typically reveals no structural abnormalities, although recent 3-T scans have demonstrated subtle changes in the basal ganglia.⁵ Genetic testing may reveal abnormalities in the DYT gene; the DYT-1 abnormality is most common and involves a three-base GAG deletion in the gene encoding the torsin A protein.⁶ Primary dystonia is rare, with the incidence of early-onset dystonia estimated to range between 2 and 50 per million. Primary dystonia often begins in children 5 to 10 years old; it starts in one lower extremity as an involuntary foot deviation and progresses slowly to affect the entire leg, then the other leg, and ultimately to become generalized in more than half of patients while remaining segmental in the remainder. The earlier the onset of dystonia, the more likely that it will become generalized and severe. The age at onset of primary dystonia is younger than 15 years in 60% of patients.

The primary-plus dystonia category is sometimes used for children with dopa-responsive dystonia (DRD, Segawa’s disease) and myoclonus-dystonia syndrome.⁴ Their biopterin and homovanillic acid levels are often low and their dopa decarboxylation is probably disordered. Some have features of parkinsonism. DRD has a diurnal variation in 75% of patients, with increased severity in late afternoon. DRD may mimic cerebral palsy (CP), with patients exhibiting movement resembling a spastic gait (but without prematurity); the distinction is critical because DRD can virtually be cured by oral levodopa.⁷ Every child with dystonia who does not have a history consistent with CP (e.g., prematurity, intraventricular hemorrhage, perinatal hypoxia) should be given a trial of oral levodopa/carbidopa for 2 to 3 months to exclude the possibility of DRD.

Heredodegenerative dystonia in children results from disorders such as Hallervorden-Spatz disease (PKAN deficiency), Wilson’s disease, Rett’s syndrome, and metabolic disorders, including disorders of lipid metabolism such as the gangliosidoses, mitochondrial disorders, and Leigh’s disease and disorders of amino acid metabolism such as glutaric aciduria. Heredodegenerative disorders are the second most common cause of pediatric dystonia and are often progressive.

Secondary dystonia results from structural abnormalities in the brain and is the most common form of pediatric dystonia by far, in whom it accounts for 80% to 90% of cases.^8–10 Most cases of secondary dystonia are associated with CP; traumatic brain injury is the second most common cause of secondary dystonia in children and stroke the third. However, any structural lesion affecting the basal ganglia, particularly cavernous malformations or tumors, may induce dystonia. The putamen is the most common site of structural abnormality (Fig. 228-1). Dystonic CP may begin in infancy or at any time during childhood, even in adolescence. It may affect the entire body or involve the upper and lower extremities while being associated with hypotonia of the neck and trunk. Dystonic CP often worsens slowly over time, although worsening is unusual after the teenage years. Posttraumatic dystonia is more likely to be focal or hemidystonic than generalized and may develop months to years after pediatric brain injury. Pediatric dystonia may also be caused by medications, including dopamine receptor blocking agents (neuroleptics), dopa mimetics (cocaine), and phenothiazines.

FIGURE 228-1 Axial magnetic resonance image of a patient with right upper extremity secondary dystonia demonstrating extensive damage to the left putamen.

Dystonia is also classified by site of involvement. Focal dystonia affects one body region, such as one upper extremity. Multifocal dystonia almost never develops in children. Segmental dystonia affects adjacent body regions, such as cervical torticollis and dystonia in an adjacent upper extremity. Hemidystonia affects one side the body and is almost always caused by a structural brain lesion. Generalized dystonia—by far the most common pediatric form of dystonia regardless of etiology—affects the entire body.

Primary dystonia can be graded with the Burke-Fahn-Marsden (BFM) scale, a validated scale developed to grade adults with primary dystonia.¹¹ Secondary dystonia can be graded with the Barry-Albright Dystonia (BAD) scale, a validated scale developed to grade children with secondary dystonia.¹² Neither scale is sensitive to the small changes in dystonia that may be of clinical significance in children.

Medical Treatment of Pediatric Dystonia

Baclofen (Lioresal), trihexyphenidyl (Artane), and carbidopa-levodopa (Sinemet) are the three mainstays of oral treatment; clonazepam, anticonvulsants (e.g., carbamazepine), and tetrabenazine are secondary medications. The fact that medications include a dopa agonist, a GABA agonist, an anticholinergic, a benzodiazepine, and a dopamine agonist suggests that the pathophysiology is either poorly understood or multifactorial. Sinemet is dramatically effective for DRD, but with that exception, oral medications are usually only mildly helpful. All are started at small doses and increased gradually—Sinemet up to 25/100 mg three times daily, baclofen up to 30 mg three times daily, and trihexyphenidyl up to 10 mg three times daily. Oral medications seem to be more effective in young children (e.g., younger than 6 years) than in older children.

Focal dystonia is often treated with intramuscular injections of botulinum toxins. There are few published reports of the use of botulinum toxins in children with dystonia, but their use is widespread to augment the more generalized effects of oral medications, particularly in children with mixed spasticity and dystonia.

Neurosurgical Treatment and Outcomes