Etiology and Clinical Manifestation of Dystonia in Children
Dystonia refers to a syndrome of involuntary sustained or spasmodic muscle contractions involving co-contraction of the agonist and the antagonist. The movements are usually slow and sustained, and they often occur in a repetitive and patterned manner; however, they can be unpredictable and fluctuate.
The frequent abnormal posturing and twisting can be painful, and the functional impact of dystonia can vary from barely noticeable to severely disabling. Consequently, dystonias can have a profound effect on the personal, vocational, and emotional life of a patient and can impact his/her ability to live independently.
The options to medically manage dystonic movements have traditionally been 4-fold; they consist of the following:
- Rehabilitative therapies
- Oral medications
- Neurochemolytic interventions
Psychological counseling and participation in support groups are vital adjuncts to medical and physical approaches in the multidisciplinary management of dystonia.
Surgical options for intractable dystonias include altering the location or length of problematic muscles, but this is rarely successful. Other techniques include transection of the spinal accessory nerve for cervical dystonia, stereotactic thalamotomy or pallidotomy for generalized dystonia, and deep brain stimulation (DBS).
Thorough neurologic, physiatric, neuropsychologic, and physical therapy evaluations are important prior to consideration for surgery. Because of the risk of significant comorbidity, surgical approaches are reserved for patients with disabling dystonia in whom other treatment modalities have been exhausted.
- Impaired basal ganglia outflow is thought to play a role in the genesis of some dystonias. Lesions in the putamen have been linked to hemidystonia. Bilateral putaminal involvement may be responsible for generalized dystonia.
- Torticollis and hand dystonia are thought to result from involvement of the head of the caudate nucleus and thalamus, respectively. Disease of the thalamus and subthalamus, as well as derangement of hypothalamic function, also has been suspected.
- Because the basal ganglia play a role in maintaining normal head posture, the basal ganglia and the vestibulo-ocular reflex pathway have been implicated in the development of cervical dystonia. Disturbances of neurotransmitter systems also have been described in dystonias. [5, 9]Abnormalities in blink reflex recovery suggest involvement of the brainstem. Cervical and upper limb traumas have been implicated as well.
- A study by McClelland et al indicated that there are significant differences in the rate and pattern of pallidal firing according to the etiology and phenotype of dystonia. For example, the median firing frequency of the internal globus pallidus was higher in patients with primary dystonia than in those with secondary static dystonia and was higher in patients with progressive dystonia secondary to neuronal brain iron accumulation than in the other two groups.
- Drug-induced supersensitivity of striatal dopamine receptors and abnormality of gamma-aminobutyric acid (GABA)–ergic neurons are proposed mechanisms for some drug-induced dystonias. Although supersensitivity is an inevitable accompaniment of long-term antipsychotic drug treatment, tardive dyskinesia does not always occur.
- Abnormalities of serotonin, dopamine, and norepinephrine in specific cerebral structures also have been associated with dystonia musculorum deformans. In a literature review of human and animal studies, Smit et al pointed out that reduced levels of the serotonin metabolite 5-hydroxyindolacetic acid have been found in association with dystonia. The investigators also identified 89 cases, reported in 49 papers, that demonstrated a relationship between dystonia and drugs that impact the serotonergic system.
History, Physical Examination, and Diagnostic Studies
- In dystonia, as in all neuromuscular disorders, history taking and physical examination are necessary. Family history is important; as many as 44% of patients have a family history of similar or other movement disorders.
- Dystonia may be a clinical manifestation of many treatable neurologic conditions; therefore, a thorough screening should be performed to exclude Wilson disease (ie, hepatolenticular degeneration), hypoxic brain injury, traumatic brain injury, Huntington disease, Leigh disease, lipid storage disease, and Parkinson disease.
- A number of medications can induce acute dystonic movements, and a careful investigation of the patient’s medication list must be performed to rule out iatrogenic causes. Common drugs that can induce movement disorders and dystonias include, but are not limited to, the following:
- Dopamine antagonists
- Valproic acid
- Dopamine agonists
- Monoamine oxidase inhibitors (MAOIs)
- Adrenergic agents
- Beta agonists
- Tricyclic antidepressants
- Oral contraceptives
Various laboratory studies should be considered in the evaluation of dystonia. Blood chemistries, liver functions, ceruloplasmin levels, and blood copper levels may be appropriate.
Magnetic resonance imaging (MRI) and computed tomography (CT) scanning of the brain are especially important in the pediatric population and may identify hypoxic, hemorrhagic, or tumorous lesions. Slit-lamp eye examination for Kayser-Fleischer rings and 24-hour urine copper analysis also may be useful.
Genetic screening for DYT gene abnormalities and genetic counseling are important for patients who have had an onset of primary dystonia before age 30 years or for persons who have an affected relative.