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ADVANCES IN PEDIATRICS
Keywords
Movement disorders Motor Hyperkinetic
Key points
Hyperkinetic movement disorders of childhood are a common presentation to the
general pediatrician and pediatric neurologist.
Pediatric movement disorders encompass both benign and self-limited conditions
as well as progressive disorders.
Classifying the phenomenology of the movement disorder is key to guiding work-
up and treatment.
Counseling the family and patient on the pathophysiology and indications for
treatment is imperative.
https://doi.org/10.1016/j.yapd.2018.04.010
0065-3101/18/ª 2018 Elsevier Inc. All rights reserved.
230 WILSON & KEENER
history; and family history, including any concern for genetic risk factors. The
next step is to classify the phenomenology of the movement disorder. At times,
viewing home video footage may be helpful. Table 1 lists the current
consensus definitions of hyperkinetic movement disorders in children. A com-
bination of movement disorders may be present; for example, children with
dyskinetic cerebral palsy often have a combination of dystonia, chorea, and
athetosis. The next step is to identify if the movement disorder is the primary
symptom or if it is occurring in the context of other neurologic, psychiatric, or
systemic symptoms. This guides further imaging and/or laboratory evaluation
and treatment.
DYSTONIA
Dystonia is characterized by involuntary sustained or intermittent muscle con-
tractions causing repetitive movements and/or abnormal postures [1]. The most
common cause of dystonia in children is dyskinetic cerebral palsy. Other sec-
ondary causes include encephalitis, vascular disease, autoimmune disease,
metabolic derrangements, and neurodegenerative diseases. Primary or idio-
pathic dystonia in children is typically genetic in etiology, with a growing list
of genetic mutations identified [2]. Table 2 lists the more common primary ge-
netic dystonias and their clinical features.
DYT-TOR1A dystonia, also known as DYT1 or Oppenheim dystonia, is an
autosomal-dominant condition with reduced penetrance and variable expres-
sion. It is the most common cause of hereditary generalized dystonia in chil-
dren, with typical onset in the first or second decade of life characterized by
Table 1
National Institutes of Health Taskforce on Childhood Movement Disorders: consensus defini-
tions of hyperkinetic movement disorders
Term Definition
Dystonia Involuntary sustained or intermittent muscle contractions causing twisting and
repetitive movements, abnormal postures, or both
Chorea Ongoing, random-appearing sequence of 1 or more discrete involuntary
movements or movement fragments
Athetosis Slow, continuous, involuntary writhing movement that prevents maintenance
of a stable posture
Myoclonus Repeated, often nonrhythmic, brief shock-like jerks due to sudden involuntary
contraction or relaxation of 1 or more muscles
Tremor Rhythmic, back-and-forth or oscillating involuntary movement about a joint
axis
Tics Repeated, individually recognizable, intermittent movements or movement
fragments that are almost always briefly suppressible and are usually
associated with awareness of an urge to perform the movement
Stereotypies Repetitive, simple movements that can be voluntarily suppressed
Data from Sanger TD, Chen D, Fehlings DL, et al. Definition and classification OF hyperkinetic movements in
childhood. doi:10.1002/mds.23088.
MOVEMENT DISORDERS IN CHILDREN 231
focal dystonia of the foot with walking. This then gradually spreads to involve
the contralateral lower limb, trunk, upper extremities, and rarely also the neck
and face. The mutation occurs more commonly among Ashkenazi Jewish pa-
tients due to a founder effect [2]. Deep brain stimulation (DBS) has been shown
an effective treatment of this form of dystonia with durable benefit [3].
Dopa-responsive dystonia, also known as Segawa syndrome, is another
autosomal-dominant condition with variable penetrance that presents in child-
hood as a predominantly lower extremity dystonia and may be accompanied
by parkinsonism. The symptoms classically demonstrate diurnal fluctuation,
worsening later in the day and after exercise. More than 100 mutations have
been identified in the GTP cyclohydrolase 1 gene (GCH1), although other
genes also are implicated [2,4]. As a result, there is a marked response to treat-
ment with levodopa. Because it may be difficult to distinguish various forms of
genetic dystonia clinically, it is recommended that all children presenting with
dystonia undertake a trial of levodopa therapy.
Symptomatic treatment of secondary or primary dystonia with medications
may include anticholinergics, benzodiazepines, baclofen, or antidopaminergic
drugs, including neuroleptics or the dopamine depleter tetrabenazine. The
side effects of these medications may limit their utility, and this often requires
an ongoing discussion that should be held with patients and their families. For
focal or segmental dystonia, botulinum toxin injections are the treatment of
choice [5]. DBS for dystonia was granted humanitarian device exemption by
the US Food and Drug Administration in 2003. The globus pallidus is the
most common target. There is strong evidence to support the use of DBS in
the treatment of primary dystonia, especially DYT1, with lesser benefit seen
in secondary dystonia due to structural lesions, such as stroke, trauma, and
perinatal hypoxic-ischemic injury [6].
CHOREA
Chorea is a hyperkinetic movement disorder characterized by involuntary,
apparently random, jerking or flowing movements. As a result, children with
chorea may appear fidgety and restless. Chorea may be seen in combination
with athetosis, which is a slower and more continuous writhing movement.
The differential diagnosis of chorea is broad, including genetic and metabolic
diseases, neurodegenerative diseases, toxins, trauma, endocrine abnormalities,
cerebrovascular disease, neoplasm, autoimmune disease, infectious, and postin-
fectious etiologies [1].
In the pediatric population, chorea may be divided into acute-subacute and
chronic presentations. The most common cause of acute pediatric chorea
worldwide is Sydenham chorea [7]. Systemic lupus erythematosus and anti-
phospholipid antibody syndrome can also cause chorea, most commonly
described in adolescence [8]. More rarely, acute chorea may occur as a result
of other infections including herpes simplex virus, Lyme disease, and HIV [9].
Sydenham chorea is an autoimmune sequelae of group A b-hemolytic
streptococcal infection and is considered a manifestation of rheumatic disease
232 WILSON & KEENER
Table 2
DYT classification of select primary genetic dystonias
DYT number Clinical features Genetics
DYT1 Early-onset, generalized dystonia, often beginning in Gene: TOR1A; AD
1 foot
DYT5a Dopa-responsive dystonia, diurnal fluctuation Gene: GCH1; AD
DYT5b Tyrosine hydroxylase deficiency Gene: TH; AR
DYT6 Adolescent-onset dystonia with mixed phenotype, Gene: THAP1; AD
prominent craniocervical component
DYT8 Paroxysmal nonkinesogenic dyskinesia Gene: MR1; AD
DYT10 Paroxysmal kinesogenic dyskinesia Gene: PRRT2; AD
DYT11 Myoclonus dystonia Gene: SGCE; AD
DYT12 Rapid-onset dystonia–parkinsonism Gene: ATP1A3; AD
DYT18 Paroxysmal exercise-induced dyskinesia Gene: SLC2A1; AD
Abbreviations: AD, autosomal dominant; AR, autosomal recessive.
Adapted from Lohmann K, Klein C. Update on genetics of dystonia. Curr Neurol Neurosci Rep 2017;17:26;
and Erro R, Sheerin UM, Bhatia KP. Paroxysmal dyskinesias revisited: a review of 500 genetically proven cases
and a new classification. Mov Disord 2014;29(9):1108–16. doi:10.1002/mds.25933; with permission.
TREMOR
Tremor is defined as a rhythmic, oscillatory movement about a joint axis
(Sanger 2010) [1]. Tremor is typically classified according to the position during
which it occurs—rest tremor, postural tremor, kinetic tremor, or isometric
tremor. Examination of a child with tremor is, therefore, directed at eliciting
the tremor in these various circumstances. Observation of daily activities,
such as writing/drawing, eating, and drinking, may also be helpful.
Essential tremor is the most common cause of tremor in adults, with approx-
imately 50% reporting onset of tremor in childhood [13]. This is characterized
by a postural and kinetic tremor, most often involving bilateral upper extrem-
ities. It also may affect the voice and head, although less commonly in children
[14]. Pediatric essential tremor is 3 times more common in boys compared with
girls [14]. A vast majority of children with essential tremor have a family his-
tory of tremor [15]. Despite this, the field of genetics of essential tremor re-
mains challenging, likely due to the phenotypic and genotypic heterogeneity
of this condition [16]. The decision to initiate pharmacologic treatment is
dependent on the degree of social or functional impairment due to tremor.
In the pediatric population, propranolol is considered the initial treatment
choice. Primidone has demonstrated efficacy in adult essential tremor,
although having little evidence in the pediatric population. Furthermore, its
metabolite phenobarbital has been shown in children with epilepsy to carry
a long-term risk of osteoporosis and disorders of cognition, mood, and
behavior. Second-line medications for essential tremor include zonisamide, top-
iramate, and gabapentin [14].
Tremor may commonly occur as a side effect of medications or secondary to
underlying metabolic or endocrine disturbances, such as hyperthyroidism
(Box 1). There is a long list of medications that can cause tremor, typically
characterized by a high-frequency postural and kinetic tremor that is rarely
234 WILSON & KEENER
TIC DISORDERS
Tic disorders include Tourette disorder (or Tourette syndrome [TS]), persis-
tent (chronic) motor or vocal tic disorder, and provisional tic disorder.
Disorders differ by presence of motor and/or vocal tics and duration of tic
symptoms.
TS is a neurodevelopmental disorder characterized by the presence of mul-
tiple motor tics and at least 1 vocal tic, which persist for at least 1 year regard-
less of tic-free periods. Persistent (chronic) motor or vocal tic disorder is
defined by having a single or multiple motor or vocal tics, but not both vocal
and motor tics, for more than 1 year. Lastly, provisional tic disorder requires
the presence of single or multiple motor and/or vocal tics that have been pre-
sent for less than 1 year. The onset of age for all tic disorders is prior to
18 years and tics cannot be attributable to a medical condition or the effect
of a substance [18].
Tics are sudden, rapid, involuntary, nonrhythmic movements or vocaliza-
tions. Tics can be either simple or complex motor or vocal tics. Simple motor
tics are of short duration and often characterized by eye blinking, neck jerk-
ing, and shoulder shrugging. Complex motor tics often seem more purpose-
ful in nature and involve multiple muscle groups; examples include
simultaneous shoulder shrugging and head turning and grimacing of face
and neck jerk. Similarly, complex vocal tics can include repeating the last
heard word or phrases, uttering socially unacceptable words, or repeating
one’s own sounds or words. Simple vocal tics are often caused by contraction
of diaphragm or oral pharynx and can include sniffing, grunting, and throat
clearing [18,19].
236 WILSON & KEENER
Treatment
The decision to treat tics is based on the level of impact of tics on social,
emotional, and adaptive functioning for a child. Mild tics often do not lead
to significant impact on overall functioning and well-being; thus, monitoring
of tic changes in tic severity is recommended. The impact of tics on overall
function is different for each individual; hence, the utility in a rating scale is
to better quantify tic severity and monitor for change when implementing an
intervention. It is imperative, however, that the first steps of treatment include
psychoeducation and counseling regarding tic phenomenology; natural patho-
physiology; effect on social, emotional, and academic functioning; behavioral
comorbidities; and therapeutic options [22]. Providing psychoeducation to pa-
tients and families can improve knowledge and attitudes of family members
and peers toward individuals with tics and TS [25].
Nonpharmacologic treatments
Behavioral interventions have had positive outcomes in treating tics. Compre-
hensive Behavioral Intervention for Tics (CBIT) has been shown efficacious in
the treatment of tics for children and adults in 2 randomized controlled clinical
trials [26,27]. The primary component of CBIT consists of habit reversal
training. Habit reversal training involves the development of tic awareness
by self-monitoring of tics and the premonitory urges associated with them.
Competing response training involves engaging in a voluntary behavior that
is physically incompatible with the tic when the urge to perform the tic occurs.
CBIT also includes relaxation training and identifying situational factors that
influence tic severity, with the development of strategies to reduce the influence
of these factors [27]. CBIT is recommended for individuals over the age of 9
with tics and generally should be considered first-line treatment [22].
Pharmacologic treatments
The most commonly used pharmacologic treatments for tics are reviewed.
Pharmacologic intervention for tics should be considered when patients require
an active intervention for tic symptoms and behavioral therapy is not available
or has had limited efficacy. Pharmacotherapy should also be initiated at a low
dose and titrated as needed.
a-Agonists (guanfacine and clonidine) are commonly used first line due to
the evidence for efficacy and a more favorable side-effect profile. Studies of
guanfacine and clonidine in children have shown larger effect sizes in children
with tics and comorbid ADHD. Common adverse effects of a-agonists include
sedation, bradycardia, and hypotension, and patients should be monitored for
these side effects. a-Agonists should be discontinued with a gradual taper to
avoid rebound hypertension [19,22,28].
Antipsychotic medications are one of the oldest treatments for tics and have
been found effective. There is support from randomized controlled trials to
238 WILSON & KEENER
STEREOTYPIES
Motor stereotypies are involuntary, repetitive, rhythmic movements that have
a predictable pattern and location and seem purposeful but do not serve an
obvious function. The movements also tend to be long occur in clusters and
are complex in nature. The complex movements are often characterized by
body rocking, hand flapping, and head nodding, and the movements can often
be suppressed [31]. Motor stereotypies are often triggered by periods of excite-
ment, stress, fatigue, boredom, or being focused on an activity. The typical age
of onset for a complex motor stereotypy (CMS) is before 3 years of age. His-
torically, these CMSs were believed to only occur in children with neurodeve-
lopmental disorders (secondary motor stereotypy) but it is now known that
these movements can occur in typically developing children as well and are
considered primary motor stereotypies [32].
The prevalence of primary CMSs is believed 2% to 4%, and symptoms can
be persistent. There is not much literature on the outcomes of CMSs, but in
children younger than 12 years of age studies have noted a complete resolution
of symptoms in 3% to 20% of individuals.
In regard to treatment, it is often recommended to monitor for improvement
over time. There have been few data to support any pharmacologic treatment
of CMSs and anecdotal data also show little benefit [33]. One study used a
combination of modified habit reversal therapy and differential reinforcement
of other behavior and showed reduction of CMSs in a small group of typically
developing children [34]. Another study used an instructional DVD designed
for parents to provide home based therapy for CMSs, and there was an effec-
tive reduction of primary motor stereotypy [33]. Overall, there remains
little evidence for pharmacologic and behavioral intervention for CMSs but
MOVEMENT DISORDERS IN CHILDREN 239
SUMMARY
Movement disorders in children are more often hyperkinetic, presenting as
excessive rather than diminished movement activity. Classification of abnormal
movements is based on specific observed features, such as dystonia, tremor,
chorea, and tics, and many of these movements can be co-occurring. It is of
utmost importance that a practitioner perform a thorough clinical evaluation
to determine the type and etiology of the abnormal hyperkinetic movements.
Once an etiology is determined, the appropriate diagnostic work-up and treat-
ment can be pursued. Significant progress continues to be made in understand-
ing the pathogenesis, underlying neurobiology, and treatment of many
hyperkinetic pediatric movement disorders. It is imperative that the family
and the child receive counseling on the etiology and natural pathophysiology
of these abnormal hyperkinetic movements and the need for intervention or
monitoring for improvement over time.
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