Dystonia consists of repetitive, patterned, twisting,
and sustained movements that may be either slow or rapid.
Dystonic states are classified as primary, secondary, or
psychogenic depending upon the cause. By definition, primary
dystonia (formerly known as dystonia musculorum deformans or
idiopathic torsion dystonia) is associated with no other
neurologic impairment, such as intellectual, pyramidal,
cerebellar, or sensory deficits. However, tremor that appears
identical to essential tremor occurs in approximately 20 percent
of patients with this condition. In some families, dystonia and
essential tremor coexist. Cerebral palsy probably is the most
common cause of secondary dystonia seen in children.
Clinical features — The onset of involuntary movements
occurs before age 20 in approximately 30 percent of patients
with dystonia. The distribution of the affected muscle groups
appears to depend upon age. The disorder typically begins
distally in children, whereas a cranial-cervical distribution is
more common in adults. Childhood dystonia usually progresses to
a generalized disorder, whereas adult dystonia usually remains
focal or segmental.
The range of severity of dystonia is variable
and may depend upon the situation. As an example, some patients
have task-specific dystonias that occur only when they
participate in certain activities, such as writing, typing, or
playing the piano ("musician's hands"). As the dystonia worsens,
it typically extends to adjacent muscles and eventually occurs
even at rest. In rare cases, the spasms become severe and may
cause cervical disc, nerve, or root problems. Muscle breakdown
with myoglobinuria ("dystonic storm") also can occur.
No specific morphologic changes have been noted in
neuropathologic examinations of patients with primary dystonia.
In the brains of a few patients, the norepinephrine
concentration was markedly reduced in the posterior and lateral
hypothalamus and increased in the red nucleus, suggesting a
neurotransmitter abnormality. However, further studies are
needed to confirm these findings. The fluorodopa positron
emission tomography (PET) scan usually is normal, although (18F)
fluorodeoxyglucose shows an abnormal pattern of metabolic
activity when data are averaged from a large group of dystonic
Genetics — Primary dystonia may be sporadic or inherited.
Cases with onset in childhood usually are inherited in an
autosomal dominant pattern. Many hereditary cases are caused by
a defect in torsinA, a protein with uncertain function that is
expressed in the brain. A rare cause of hereditary dystonia is
TorsinA mutation — Many patients with hereditary dystonia have a
mutation in the TOR1A (DYT1) gene that encodes the protein
torsinA, a novel ATP-binding protein in the 9q34 locus. TorsinA
is expressed widely in the brain, particularly in the
hippocampus, substantia nigra pars compacta, and cerebellum.
Almost all patients have a three base pair deletion that results
in loss of a glutamic acid residue in the C-terminal region of
the torsinA protein.
The role of torsinA in the pathogenesis of primary dystonia is
unknown. In cultured mouse cells, distribution of the mutant and
normal protein differed; the mutant protein accumulated in
multiple large inclusions in the cytoplasm around the nucleus
rather than distributing throughout the cytoplasm. DNA testing
for the abnormal TOR1A gene can be performed on individuals with
Dopa-responsive dystonia — Dopa-responsive dystonia (DRD)
is an unusual form of hereditary progressive dystonia that
begins during the first decade after birth. The dystonia usually
starts in the legs and becomes generalized. Some patients may
also have hyperreflexia, rigidity, tremor, and other
parkinsonian features, and less commonly, cerebellar signs. The
severity of the disorder has a diurnal variation in many
patients who may be asymptomatic in the morning or after a nap,
but become increasingly fatigued with dystonic movements during
the day. The characteristic feature of DRD is the marked
improvement after treatment with levodopa or dopamine agonists.
Affected patients also respond to anticholinergic therapy.
DRD is inherited in an autosomal dominant pattern, although it
has a 3:1 female preponderance. Several mutations in the
GTP-cyclohydrolase I (GCHI) gene on chromosome 14 have been
identified in patients with DRD. GTP-cyclohydrolase I catalyzes
the first step in the synthesis of tetrahydrobiopterin (BH4),
the natural cofactor for tyrosine hydroxylase. This gene defect
results in impaired synthesis of dopamine by nigral neurons
without neuronal degeneration.
Paroxysmal dystonia — Two forms of paroxysmal dyskinesias
occur: paroxysmal kinesigenic and nonkinesigenic dystonia. The
kinesigenic form is precipitated by a sudden movement, such as
rising rapidly from a chair or turning suddenly. This disorder
predominantly affects boys and presents at 5 to 15 years of age.
The dystonia often is asymmetric and associated with
choreoathetosis and epilepsy. The attacks typically last a few
seconds and recur as often as 100 times a day. Most patients
with kinesigenic dystonia improve with anticonvulsant therapy,
including phenytoin, carbamazepine, and barbiturates.
In the nonkinesigenic disorder, which may begin in infancy,
dystonia occurs spontaneously. Episodes last minutes to hours
and recur two or three times a month. Alcohol, coffee, fatigue,
stress, exercise, or excitement may be precipitating factors.
Many affected patients also have choreoathetosis and ataxia,
especially during the attacks. Nonkinesigenic dystonia is
resistant to pharmacologic therapy, although some patients
improve with clonazepam, oxazepam, acetazolamide, valproate,
carbamazepine, and haloperidol.
Hemidystonia — Hemidystonia (also known as unilateral
dystonia) involves one-half of the body and occurs frequently in
children and young adults. Approximately 75 percent of patients
with hemidystonia have a structural lesion in the contralateral
basal ganglia, often the putamen, that resulted from an insult
to the brain. Causes associated with these lesions are
infarction or hemorrhage (30 percent) and perinatal trauma (20
percent). Hemidystonia often presented several years after the
precipitating factor; this delay occurred more often in
Drug reaction — An acute dystonic reaction that usually
is transient is a recognized complication of the dopamine
receptor-blocking drugs, such as the antipsychotics (eg,
haloperidol, chlorpromazine) and antiemetics (eg,
phenothiazines, metoclopramide), and also can occur with
levodopa, anticonvulsants, and ergots. The offending drug should
be discontinued. Patients treated with dopamine
receptor-blocking agents occasionally develop persistent tardive
dystonia after the offending drug is stopped. If no spontaneous
improvement occurs, they may respond to trials of muscle
relaxants, anticholinergic drugs, and tetrabenazine.
Other causes — Other causes of paroxysmal or fluctuating
dystonia in children include gastroesophageal reflux (Sandifer
syndrome), multiple sclerosis, thyrotoxicosis, metabolic
disorders (eg, Hartnup disease), paroxysmal dystonia in sleep
(hypnogenic dystonia), and "infectious torticollis." Dystonia
may be erroneously attributed to a postural deformity that
results from common musculoskeletal or orthopedic problems such
as congenital torticollis or scoliosis. The number of cases of
these disorders that actually represent dystonia is not known.
Treatment — Appropriate treatment of dystonia depends
upon an accurate diagnosis. Patients with atypical features,
such as impaired intellect, seizures, neuro-ophthalmologic
abnormalities, ataxia, corticospinal tract signs, sensory
deficits, severe speech disturbance, and unilateral distribution
of the dystonia, are more likely to have an underlying disorder
that can be treated, such as Wilson disease.
All patients with childhood-onset dystonia, especially those
with parkinsonian features, should be treated with levodopa
because they may have DRD. Anticholinergic therapy in high doses
(eg, 30 to 60 mg/day of trihexyphenidyl) is effective in
approximately two-thirds of children with primary dystonia.
Trihexyphenidyl is introduced in small doses (1 mg bid) and
gradually increased by 2 to 4 mg per week over several weeks or
months until symptoms improve or side effects (eg, mental
dullness, blurred vision, or other anticholinergic reactions)
prevent further increases.
Tetrabenazine, a monoamine-depleting agent, is effective in some
patients with dystonia (including 63 percent of those with
primary dystonia); sometimes it is combined with pimozide, a
postsynaptic dopamine receptor-blocking drug, and the
anticholinergics. Other drugs that sometimes are effective
include oral and intrathecal baclofen, carbamazepine, valproate,
primidone, and lithium.
Botulinum toxin injections are given when pharmacologic therapy
fails, and may be most helpful in patients with focal dystonia.
— Deep brain stimulation (DBS) of the
internal globus pallidus (GPi) has emerged as the
surgical treatment of choice for patients with disabling
dystonia who do not respond to pharmacologic therapy or
chemodenervation with botulinum toxin. In a randomized
controlled trial that evaluated 40 patients with primary
segmental or generalized dystonia, bilateral DBS of the GPi was
significantly more effective than sham stimulation at three
months for improvement in the severity of dystonia, reduction in
disability, and improvement in the physical aspects of quality
Since the advent of DBS, stereotactic thalamotomy, pallidotomy,
and cervical rhizotomy are rarely used to treat refractory